A search conducted at Indiana University, Bloomington, Indiana
TI: Heat shock and cytokines modulate the expression of adhesion molecules on different human gastric-cancer cell lines.
AU: Hsieh-MC; Wu-CW; Wu-LH; Lui-WY; P'eng-FK; Yu-CL
AD: Department of Surgery, Veterans General Hospital-Taipei, National Yang-Ming University School of Medicine, Republic of China.
SO: Int-J-Cancer. 1996 Sep 4; 67(5): 690-4
ISSN: 0020-7136
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: In order to understand the expression and modulation of adhesion molecules (AMs) on the surface of different gastric cancers, we studied 4 gastric-cancer cell lines including SC-M1, KATO-III, AGS and AZ-521. The expression of E-cadherin, integrins (beta1, beta2 and beta3), ICAMs (1 and 2), and CD11 (a, b and c) on the cells was detected by flow cytometry. We found that E-cadherin was only expressed on SC-M1 and KATO-III. CD29 (beta1 integrin) could be found in cells of all 4 lines. CD54 (ICAM- 1) could not be detected in AZ-521. In contrast, CD18 (beta2 integrin), CD61 (beta3 integrin), ICAM-2, CD11a, CD11b and CD11c were all absent from these cells. Heat-shock treatment (42.5 degrees C, 60 min) enhanced the expression of E-cadherin, CD29 and CD54 on SC-M1, and of CD29 on AGS. In addition, TNF-alpha (50U/ml) and IL-1beta (10U/ml) modulated the expression of these AMs, like heat-shock treatment. The increment of these adhesion molecules caused by heat shock, TNF-alpha and IL-1beta stimulation on SC-M1 was also confirmed by Western blot analysis. Functionally, these treatments increased the binding between normal human mononuclear cells and SC-Ml cells. The heat-shock treatment could induce a significant amount of TNF-alpha and IL-1beta release from SC-M1 and KATO-III, but seemed irrelevant to the expression of AMs. These results suggest that limited adhesion molecules were expressed on the surface of different gastric cancer cells. Heat shock, IL-1beta and TNF-alpha may selectively modulate the expression of these 3 molecules on some of the cells, and this is probably related to their antitumor effect.
MESH: Antigens,-CD-metabolism; Antigens,-CD11-metabolism; Blotting,-Western; Cadherins-metabolism; Flow-Cytometry; Integrins-metabolism; Intercellular-Adhesion-Molecule-1-metabolism; Interleukin-1-pharmacology; Tumor-Cells,-Cultured; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Adhesion-Molecules-metabolism; *Cytokines-pharmacology; *Heat-; *Stomach-Neoplasms-metabolism
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: intercellular-adhesion-molecule-2; Antigens,-CD; Antigens,-CD11; Cadherins; Cell-Adhesion-Molecules; Cytokines; Integrins; Interleukin-1; Tumor-Necrosis-Factor; Intercellular-Adhesion-Molecule-1
AN: 96376788
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 2 of 125
TI: Fibronectin modulates interleukin 6 and fibronectin synthesis of human glomerular mesangial cells in culture.
AU: Schieren-G; Burger-A; Braunger-M; Filsinger-S; Hansch-GM
AD: Institut fur Immunologie der Universitat Heidelberg, Deutschland.
SO: Exp-Nephrol. 1996 Jan-Feb; 4(1): 48-55
ISSN: 1018-7782
PY: 1996
LA: ENGLISH
CP: SWITZERLAND
AB: In this paper we report that fibronectin (FN) and its proteolytic 120-kD fragment regulate synthesis and secretion of interleukin 6 (IL-6) and of FN by human glomerular mesangial cells. While intact FN and a fragment derived from the heparin-binding domain had no effect on IL-6 secretion, the 120-kD FN fragment containing the cell attachment site stimulated secretion by 40-fold. The same FN fragment reduced FN secretion and the steady state mRNA level by 80%. The intact FN showed only a weak inhibitory effect (+/- 30%); the 30-kD fragment containing the heparin-binding domain had no effect. The effects of the 120-kD FN were inhibited by the peptide RGDS, implying participation of the cell attachment site in signal transduction. An antibody to the alpha-chain of VLA-3 mimicked the effect of the 120-kD FN, whereas an antibody to the alpha-chain of VLA-5 was partly inhibitory. Taken together, the data suggest that FN by interacting with its receptors differentially regulates the protein synthesis of glomerular mesangial cells, promoting IL-6 secretion and inhibiting FN synthesis.
MESH: Antibodies-pharmacology; Cells,-Cultured; Fibronectins-genetics; Glomerular-Mesangium-drug-effects; Integrins-antagonists-and-inhibitors; Integrins-physiology; Oligopeptides-pharmacology; Peptide-Fragments-pharmacology; Receptors,-Fibronectin-antagonists-and-inhibitors; Receptors,-Fibronectin-physiology; RNA,-Messenger-metabolism
MESH: *Fibronectins-biosynthesis; *Fibronectins-pharmacology; *Glomerular-Mesangium-metabolism; *Interleukin-6-biosynthesis
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 91037-65-9
NM: integrin-alpha3beta1; Antibodies; Fibronectins; Integrins; Interleukin-6; Oligopeptides; Peptide-Fragments; Receptors,-Fibronectin; RNA,-Messenger; arginyl-glycyl-aspartyl-serine
AN: 96380587
UD: 9612
MEDLINE EXPRESS (R) 1/96-12/96 3 of 125
TI: Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
AU: Bazzoni-G; Carlesso-N; Griffin-JD; Hemler-ME
AD: Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
SO: J-Clin-Invest. 1996 Jul 15; 98(2): 521-8
ISSN: 0021-9738
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Cell adhesion to the extracellular matrix is largely mediated by adhesion molecules of the integrin family and is often diminished upon oncogenic transformation. However, we show here that the chronic myelogenous leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not to increased surface expression. In parallel, Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates integrin-dependent cell adhesion, by a mechanism involving increased ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin.
MESH: Cell-Line; Fibronectins-; Fusion-Proteins,-bcr-abl-physiology; Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; Immunoblotting-; Interleukin-3-pharmacology; Kinetics-; Leukemia,-Experimental; Leukemia,-Megakaryocytic,-Acute; Mice-; Receptors,-Fibronectin-physiology; Receptors,-Lymphocyte-Homing-physiology; Recombinant-Proteins-biosynthesis; Recombinant-Proteins-metabolism; Time-Factors; Transfection-; Tumor-Cells,-Cultured; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Cell-Adhesion; *Fusion-Proteins,-bcr-abl-biosynthesis; *Hematopoietic-Stem-Cells-physiology; *Integrins-physiology
TG: Animal; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA42368CANCI; CA66996CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 83869-56-1
NM: integrin-alpha4beta1; Fibronectins; Fusion-Proteins,-bcr-abl; Integrins; Interleukin-3; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing; Recombinant-Proteins; Vascular-Cell-Adhesion-Molecule-1; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96331260
UD: 9611
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 4 of 125
TI: HST-1/FGF-4 stimulates proliferation of megakaryocyte progenitors synergistically and promotes megakaryocyte maturation.
AU: Konishi-H; Ochiya-T; Yasuda-Y; Sakamoto-H; Muto-T; Sugimura-T; Terada-M
AD: Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
SO: Oncogene. 1996 Jul 4; 13(1): 9-19
ISSN: 0950-9232
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: Megakaryocyte (MK) development is dependent on the complex interaction of MK progenitors, various cytokines and stromal elements. We previously reported that an injection of replication-deficient adenovirus containing HST-1/FGF-4 cDNA (Adex1HST-1) into mice caused a twofold increase in peripheral platelet count for 30 days without any other hematological or histological abnormality. In the present study using Adex1HST-1-infected human megakaryocytic Dami cells, we demonstrated for the first time that HST-1/FGF-4 promoted MK maturation, inducing increases in DNA ploidy, cytoplasmic and membrane maturation, and platelet-like particle release. Moreover, HST-1/FGF-4 acted on megakaryocytic cells to induce secretion of IL-6 and TNF-alpha, and increased adhesion of megakaryocytic cells to human endothelial cells primarily via VLA-4 and LFA-1 molecules; both mechanisms have been shown to lead to MK maturation. We also showed that HST-1/FGF-4 stimulates the proliferation of MK progenitors not alone but synergistically with IL-3 via IL-6 and with c-mpl ligand (thrombopoietin) not via IL-6. This result supports the hypothesis of the presence of two distinct populations of MK progenitors: IL-3-dependent and Tpo-dependent. All these results suggest that HST-1/FGF-4 can regulate MK development not only as an MK potentiating factor, but also as an inducer of cytokine secretion from MK, and as a modulator of adhesive interactions with endothelial cells.
MESH: Adenoviruses,-Human-genetics; Amino-Acid-Sequence; Cell-Adhesion-drug-effects; Cell-Differentiation-drug-effects; Cell-Division-drug-effects; Cell-Line; Drug-Synergism; DNA-Replication; Endothelium,-Vascular-cytology; Fibroblast-Growth-Factor-genetics; Fibroblast-Growth-Factor-pharmacology; Genetic-Vectors-genetics; Integrins-metabolism; Interleukin-3-pharmacology; Interleukin-6-pharmacology; Interleukin-6-physiology; Lymphocyte-Function-Associated-Antigen-1-metabolism; Mice-; Mice,-Inbred-BALB-C; Molecular-Sequence-Data; Ploidies-; Proto-Oncogene-Proteins-genetics; Proto-Oncogene-Proteins-pharmacology; Receptors,-Lymphocyte-Homing-metabolism; Recombinant-Fusion-Proteins-metabolism; Recombinant-Fusion-Proteins-pharmacology; Thrombopoietin-pharmacology; Tumor-Necrosis-Factor-pharmacology; Tumor-Necrosis-Factor-secretion; Umbilical-Veins
MESH: *Fibroblast-Growth-Factor-physiology; *Megakaryocytes-cytology; *Proto-Oncogene-Proteins-physiology
TG: Animal; Comparative-Study; Human; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 62031-54-3; 9014-42-0
NM: integrin-alpha4beta1; proto-oncogene-protein-kfgf; Genetic-Vectors; Integrins; Interleukin-3; Interleukin-6; Lymphocyte-Function-Associated-Antigen-1; Proto-Oncogene-Proteins; Receptors,-Lymphocyte-Homing; Recombinant-Fusion-Proteins; Tumor-Necrosis-Factor; Fibroblast-Growth-Factor; Thrombopoietin
AN: 96292222
UD: 9611
MEDLINE EXPRESS (R) 1/96-12/96 5 of 125
TI: Leukocyte activation study during occlusive arterial disease of the lower limb: effect of pentoxifylline infusion.
AU: Fossat-C; Fabre-D; Alimi-Y; Bienvenu-J; Aillaud-MF; Lenoble-M; Juhan-Vague-I; Juhan-C
AD: Laboratoire d'Hematologie, CHU Timone, Marseille, Puteaux, France.
SO: J-Cardiovasc-Pharmacol. 1995; 25 Suppl 2: S96-100
ISSN: 0160-2446
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Granulocytes play a significant role in vascular diseases. The mechanisms of neutrophil-mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators. Pentoxifylline (PTX) has a well-demonstrated ability to act on the activated neutrophils. It increases chemotaxis and decreases their adherence to endothelial cells, oxidative burst, and enzyme release. In this preliminary study, we investigated the effects of PTX on ischemia-induced changes in polymorphonuclear neutrophils (PMN) activation and cytokine release. A double-blind, randomized, placebo-controlled trial was carried out in 14 patients (age range 46-86 years) suffering from critical ischemia, as defined by the European Consensus Document, or subacute ischemia due to occlusive arterial disease of the lower limb. Femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before (TO) and after infusion (T24) of PTX or placebo. PMN activation was evaluated by study of cell migration, beta 2 integrin expression (CD11b/ CD18), oxidative burst, and elastase release. Inflammation proteins were analyzed, such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), C-reactive protein (CRP), and fibrinogen. Before treatment, our results demonstrate an important activation in both femoral and antecubital venous blood. PMN activation markers, cytokine release, and other inflammation proteins were significantly increased compared with normal subjects. In the experimental group there was no significant difference between femoral and antecubital venous blood. Six patients received PTX infusion and seven patients were in the placebo group. The effect of PTX was evaluated after 24 h of treatment (1,200 mg). In the PTX group the following variables were improved compared with the placebo group: CD11b expression on PMNs, elastase released from PMNs, fibrinogen, CRP, TNF-alpha, and IL6 in plasma. These preliminary results should be interpreted with caution because of the small sample size. Further trials may contribute to more complete understanding.
MESH: Aged-; Aged,-80-and-over; Biological-Markers; Cell-Adhesion-drug-effects; Chemotaxis,-Leukocyte-drug-effects; Cytokines-metabolism; Double-Blind-Method; Hydrogen-Peroxide-blood; Integrins-biosynthesis; Leg-blood-supply; Leukocytes-drug-effects; Middle-Age; Neutrophils-drug-effects; Neutrophils-metabolism; Regional-Blood-Flow-drug-effects
MESH: *Arterial-Occlusive-Diseases-blood; *Leukocytes-metabolism; *Macrophage-Activation-drug-effects; *Pentoxifylline-pharmacology; *Vasodilator-Agents-pharmacology
TG: Human; Male; Support,-Non-U.S.-Gov't
PT: CLINICAL-TRIAL; JOURNAL-ARTICLE; RANDOMIZED-CONTROLLED-TRIAL
RN: 0; 0; 0; 0; 6493-05-6; 7722-84-1
NM: Biological-Markers; Cytokines; Integrins; Vasodilator-Agents; Pentoxifylline; Hydrogen-Peroxide
AN: 96234434
UD: 9611
MEDLINE EXPRESS (R) 1/96-12/96 6 of 125
TI: Cytokine regulation of proliferation and cell adhesion are correlated events in human CD34+ hemopoietic progenitors.
AU: Levesque-JP; Haylock-DN; Simmons-PJ
AD: Department of Haematology, Hanson Centre for Cancer Research, Adelaide,Australia.
SO: Blood. 1996 Aug 15; 88(4): 1168-76
ISSN: 0006-4971
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesive interactions with the extracellular matrix of the bone marrow (BM) stroma are of critical importance in the regulation of hematopoiesis. In part, these interactions are presumed to play an important role in retaining CD34+ hematopoietic progenitor cells (HPCs) within the BM environment, in close proximity with BM stromal cells and the cytokines they produce. Evidence of a more direct role for cell adhesion in the regulation of hematopoiesis is provided by recent data showing that adhesive interactions can also provide important costimulatory signals. We have previously shown that normal CD34+ HPCs express high levels of fibronectin (Fn) receptors very late antigen-4 (VLA-4) and VLA-5 in a low-affinity state, which do not allow HPCs to strongly adhere on immobilized Fn, and that cytokines such as interleukin-3, granulocyte-monocyte colony-stimulating factor, and stem cell factor transiently activate these receptors, providing HPCs with an adhesive phenotype on Fn. Thus, knowledge of the functional states of adhesion receptors is critical to our understanding of the physiological mechanisms responsible for the regulation of normal hematopoiesis. Herein, we show that combinations of cytokines that synergize to stimulate the proliferation of CD34+ HPCs result in additive stimulation of the adhesion of these cells to Fn. Thus, the activation level of Fn receptors expressed by normal CD34+ HPCs is highly correlated with their proliferative state, suggesting a functional link between these two events. Therefore, we propose a 2-step model with an initial activation of VLA-4 and VLA-5 generated by cytokine receptors that is followed by a secondary signal resulting from Fn binding to VLA-4 and VLA-5, which may cooperate with those generated by cytokine receptors.
MESH: Adult-; Bone-Marrow-cytology; Cell-Adhesion; Cell-Division; Cells,-Cultured; Fibronectins-physiology; Receptors,-Cytokine
MESH: *Cell-Adhesion-Molecules-physiology; *Cytokines-physiology; *Hematopoietic-Stem-Cells-cytology; *Integrins-physiology; *Receptors,-Fibronectin-physiology; *Receptors,-Lymphocyte-Homing-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0
NM: integrin-alpha4beta1; Cell-Adhesion-Molecules; Cytokines; Fibronectins; Integrins; Receptors,-Cytokine; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing
AN: 96329548
UD: 9611
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 7 of 125
TI: Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes.
AU: Agis-H; Fureder-W; Bankl-HC; Kundi-M; Sperr-WR; Willheim-M; Boltz-Nitulescu-G; Butterfield-JH; Kishi-K; Lechner-K; Valent-P
AD: Department of Internal Medicine I, University of Vienna, Austria.
SO: Immunology. 1996 Apr; 87(4): 535-43
ISSN: 0019-2805
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: Mast cells (MC), blood basophils (Ba) and monocytes (Mo) are of haemopoietic origin. Lineage-relationships and transdifferentiation between MC and Mo, or MC and Ba, have been considered, based on common expression of antigens. In this study, comparative phenotypic analyses on MC, Ba and Mo and on respective cell lines were performed using monoclonal antibodies (mAb) to previously defined and novel CD antigens (CD1-130). By cluster analysis, the overall (all 130 CD) phenotypic relationships (given as similarity indices, SI), between primary cells (MC, Ba and Mo) and corresponding cell lines (HMC-1, KU-812, U937) were 0.716, 0.779 and 0.757, respectively. When primary cells were compared, lower SI values were found (MC versus Ba, 0.509; MC versus Mo, 0.625; Mo versus Ba, 0.698). More distant relationships were found between MC versus Ba and MC versus Mo, compared with Ba versus Mo, for adhesion receptor (R)-, complement R- and cytokine R profiles. Analysis of cytokine R revealed most significant dissimilarities between MC versus Ba and MC versus Mo (SI < 0.2). Moreover, in contrast to other CD subgroups and other lineages, MC and HMC-1 differed from each other in cytokine R expression (SI = 0.286). Cytokine R detectable on HMC-1 but not MC were granulocyte-macrophage colony-stimulating factor (GM-CSFR)alpha(CD116), CD40, Apo-1/FAS(CD95) and gp130(CD130). Cytokine R detectable on Ba but not MC, were interleukin-3 (IL-3)R alpha(CD123), IL-1RII(CD121b), IL-2R alpha(CD25) and CD40. In summary, MC, Ba and Mo display a unique CD profile with MC being the most distantly related cell. The most significant mismatch within a given lineage is the loss of cytokine R on mature MC as compared with normal myeloid progenitors and HMC-1 cells.
MESH: Basophils-immunology; Cell-Culture; Fluorescent-Antibody-Technique; Immunophenotyping-; Integrins-analysis; Mast-Cells-immunology; Monocytes-immunology; Receptors,-Cytokine-analysis; Receptors,-Fc-analysis; Receptors,-Immunologic-analysis
MESH: *Antigens,-CD-analysis; *Basophils-classification; *Mast-Cells-classification; *Monocytes-classification
TG: Comparative-Study; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: Antigens,-CD; Integrins; Receptors,-Cytokine; Receptors,-Fc; Receptors,-Immunologic
AN: 96256135
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 8 of 125
TI: Inactivation of the integrin beta 6 subunit gene reveals a role of epithelial integrins in regulating inflammation in the lung and skin.
AU: Huang-XZ; Wu-JF; Cass-D; Erle-DJ; Corry-D; Young-SG; Farese-RV Jr; Sheppard-D
AD: Lung Biology Center, University of California, San Francisco 94143, USA.
SO: J-Cell-Biol. 1996 May; 133(4): 921-8
ISSN: 0021-9525
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: The integrin alpha v beta 6 is only expressed in epithelial cells. In healthy adult epithelia, this receptor is barely detectable, but expression is rapidly induced following epithelial injury. Mice homozygous for a null mutation in the gene encoding the beta 6 subunit had juvenile baldness associated with infiltration of macrophages into the skin, and accumulated activated lymphocytes around conducting airways in the lungs. Beta 6-/- mice also demonstrated airway hyperresponsiveness to acetylcholine, a hallmark feature of asthma. These results suggest that the epithelial integrin alpha v beta 6 participates in the modulation of epithelial inflammation. Genetic or acquired alterations in this integrin could thus contribute to the development of inflammatory diseases of epithelial organs, such as the lungs and skin.
MESH: Alopecia-genetics; Alopecia-immunology; Base-Sequence; Cell-Line; Cell-Movement; Cells,-Cultured; DNA-Primers; Guinea-Pigs; Integrins-genetics; Interferon-Type-II-biosynthesis; Interleukin-4-biosynthesis; Keratinocytes-cytology; Keratinocytes-immunology; Lung-cytology; Lymphocyte-Transformation; Lymphocytes-immunology; Macrophages-immunology; Mice-; Mice,-Inbred-C57BL; Molecular-Sequence-Data; Mutation-; Skin-cytology; Stem-Cells-cytology; Stem-Cells-immunology
MESH: *Inflammation-Mediators-immunology; *Integrins-immunology; *Lung-immunology; *Skin-immunology
TG: Animal; Female; Human; Male; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HLA133259HLNHLBI; HL47412HLNHLBI; HL53949HLNHLBI
RN: 0; 0; 0; 0; 0; 82115-62-6
NM: integrin-alphavbeta6; DNA-Primers; Inflammation-Mediators; Integrins; Interleukin-4; Interferon-Type-II
AN: 96234678
UD: 9610
MEDLINE EXPRESS (R) 1/96-12/96 9 of 125
TI: Integrin signaling to NF-kappa B in monocytic leukemia cells is blocked by activated oncogenes.
AU: Rosales-C; Juliano-R
AD: Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, 27599, USA.
SO: Cancer-Res. 1996 May 15; 56(10): 2302-5
ISSN: 0008-5472
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Integrin-mediated signals play an important but poorly understood role in regulating the growth and behavior of tumor cells. In monocytes and monocytic leukemia cells, integrin-mediated adhesion results in a strong induction of a set of immediate early genes that are characteristic of monocytic differentiation and contain consensus NF-kappa B elements in their 5' regulatory regions. To investigate the role of integrin signaling in control of differentiation in a human monocytic leukemia cell line, THP-1 cells were transiently transfected with an NF-kappa B driven CAT reporter gene. Adhesion to fibronectin or cross-linking of beta1 integrins resulted in an NF-kappa B-dependent induction of CAT activity. To evaluate whether integrin signaling in this system intersects with the Ras signal transduction cascade, THP-1 cells were cotransfected with the NF-kappa B reporter and with plasmids that direct the synthesis of normal or mutant forms of Ras or Raf. We found that Ras or Raf dominant negative mutants did not inhibit integrin-mediated activation of the NF-kappa B-driven reporter. However, cotransfection with activated Ras, or with several other cytoplasmic oncogenes, blocked this process. This suggests that in monocytic leukemia cells, an antagonism exists between the mitogenic signals provided by oncogenes and the signals generated by integrin ligation. This antagonism may play an important role in regulating the balance between proliferation and differentiation in monocytic leukemias.
MESH: Cell-Adhesion; Cell-Differentiation-genetics; Cell-Division-genetics; Chloramphenicol-Acetyltransferase-biosynthesis; Chloramphenicol-Acetyltransferase-genetics; Fibronectins-metabolism; Genes,-ras; Genes,-Reporter; Interleukin-8-genetics; Monocytes-pathology; Protein-Serine-Threonine-Kinases-genetics; Proto-Oncogene-Proteins-genetics; Transfection-; Tumor-Cells,-Cultured
MESH: *Gene-Expression-Regulation,-Leukemic; *Genes,-Immediate-Early; *Integrins-physiology; *Leukemia,-Monocytic,-Acute-pathology; *Neoplasm-Proteins-physiology; *NF-kappa-B-metabolism; *Oncogenes-; *Protein-Serine-Threonine-Kinases-physiology; *Proto-Oncogene-Protein-p21ras-physiology; *Proto-Oncogene-Proteins-physiology; *Signal-Transduction-genetics
TG: Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: GM26165GMNIGMS; NHLBI45100
RN: EC 2.3.1.28; EC 2.7.10; EC 2.7.10.-; 0; 0; 0; 0; 0; 0; 0
NM: Chloramphenicol-Acetyltransferase; Protein-Serine-Threonine-Kinases; proto-oncogene-protein-mil; Fibronectins; Integrins; Interleukin-8; Neoplasm-Proteins; NF-kappa-B; Proto-Oncogene-Protein-p21(ras); Proto-Oncogene-Proteins
AN: 96200311
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 10 of 125
TI: The role of cytokines, adhesion molecules, and chemokines in interleukin-2-induced lymphocytic infiltration in C57BL/6 mice.
AU: Anderson-JA; Lentsch-AB; Hadjiminas-DJ; Miller-FN; Martin-AW; Nakagawa-K; Edwards-MJ
AD: Department of Surgery, J. Graham Brown Cancer Center, University of Louisville School of Medicine, Kentucky 40292, USA.
SO: J-Clin-Invest. 1996 Apr 15; 97(8): 1952-9
ISSN: 0021-9738
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: IL-2 mediates the regression of certain malignancies, but clinical use is limited because of associated toxicities, including parenchymal lymphocytic infiltration with multiple organ failure. Secondarily induced cytokines are important mediators of IL-2 toxicity and IL-2-induced lymphocyte-endothelial adherence and trafficking. The recently discovered C-C chemokines, RANTES (regulated on activation, normal T expressed and secreted) and macrophage inflammatory protein-1alpha, have also been implicated in lymphocytic migration. We hypothesized that IL-2 alters cytokine, C-C chemokine, and adhesion molecule expression in association with parenchymal lymphocytic infiltration. C57BL/6 mice were injected with 3x10(5) IU of IL-2 or 0.1 ml of 5% dextrose intraperitoneally every 8 h for 6 d, then killed. IL-2 induced massive lymphocytic infiltration in the liver and lung and moderate infiltration in the kidney in association with organ edema and dysfunction. Immunostaining showed increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in association with this organ-specific lymphocytic infiltration. Flow cytometry showed increased expression of the corresponding ligands (lymphocyte function-associated antigen-1 and very late antigen-4) on splenocytes. IL-2 increased TNF-alpha mRNA and protein expression in the liver. Organs infiltrated by lymphocytes had increased TNF-alpha mRNA, whereas RANTES mRNA was increased in all organs, regardless of lymphocytic infiltration. IL-2 toxicity involves organ-specific TNF-alpha and RANTES production with increased ICAM-1 and VCAM-1 expression as potential mechanisms facilitating lymphocytic infiltration and organ dysfunction.
MESH: Base-Sequence; DNA-Primers; Integrins-biosynthesis; Intercellular-Adhesion-Molecule-1-biosynthesis; Kidney-immunology; Liver-immunology; Lung-immunology; Lymphocytes-drug-effects; Mice-; Mice,-Inbred-C57BL; Molecular-Sequence-Data; Myocardium-immunology; Organ-Specificity; Polymerase-Chain-Reaction; Receptors,-Lymphocyte-Homing-biosynthesis; Recombinant-Proteins-pharmacology; RANTES-biosynthesis; Tumor-Necrosis-Factor-biosynthesis; Vascular-Cell-Adhesion-Molecule-1-biosynthesis
MESH: *Cell-Adhesion-Molecules-biosynthesis; *Chemokines-biosynthesis; *Cytokines-biosynthesis; *Gene-Expression-drug-effects; *Interleukin-2-pharmacology; *Lymphocytes-immunology
TG: Animal; Comparative-Study; Female; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA57527CANCI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Cell-Adhesion-Molecules; Chemokines; Cytokines; DNA-Primers; Integrins; Interleukin-2; Receptors,-Lymphocyte-Homing; Recombinant-Proteins; RANTES; Tumor-Necrosis-Factor; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96194696
UD: 9608
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 11 of 125
TI: VLA-5-mediated interaction with fibronectin induces cytokine production by human chondrocytes.
AU: Yonezawa-I; Kato-K; Yagita-H; Yamauchi-Y; Okumura-K
AD: Department of Orthopedic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
SO: Biochem-Biophys-Res-Commun. 1996 Feb 6; 219(1): 261-5
ISSN: 0006-291X
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Adhesion molecules of the integrin family, including very late activation antigens (VLA), have been implicated in various cellular functions. In this study, we investigated the contribution of integrin-mediated interaction with ECM proteins to the cytokine gene expression in human chondrocytes. Human articular chondrocytes expressed VLA-1, -2, -3 and -5 on the cell surface, and could adhere to various ECM proteins, especially to fibronectin (FN). Furthermore, the production of GM-CSF and IL-6 was potently induced by culturing chondrocytes on immobilized FN. This stimulative effect of FN was completely inhibited by an anti-integrin alpha 5 chain mAb, as well as by anti-integrin beta 1 chain mAbs. These results indicate an important role of the VLA-5-mediated interaction with FN in regulating inflammatory cytokine production by human articular chondrocytes.
MESH: Antibodies,-Monoclonal-pharmacology; Cartilage,-Articular-metabolism; Cell-Adhesion; Cells,-Cultured; Collagen-pharmacology; Extracellular-Matrix-Proteins-pharmacology; Gene-Expression; Granulocyte-Macrophage-Colony-Stimulating-Factor-biosynthesis; Integrins-analysis; Interleukin-6-biosynthesis; Macromolecular-Systems; Mice-; Rats-; Receptors,-Fibronectin-immunology; RNA,-Messenger-analysis; RNA,-Messenger-biosynthesis
MESH: *Cartilage,-Articular-immunology; *Cytokines-biosynthesis; *Fibronectins-pharmacology; *Integrins-biosynthesis; *Receptors,-Fibronectin-physiology
TG: Animal; Comparative-Study; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 83869-56-1; 9007-34-5
NM: Antibodies,-Monoclonal; Cytokines; Extracellular-Matrix-Proteins; Fibronectins; Integrins; Interleukin-6; Macromolecular-Systems; Receptors,-Fibronectin; RNA,-Messenger; Granulocyte-Macrophage-Colony-Stimulating-Factor; Collagen
AN: 96190703
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 12 of 125
TI: Influence of cytokine stimulation (granulocyte macrophage-colony stimulating factor, interleukin-3 and transforming growth factor-beta-1) on adhesion molecule expression in normal human bone marrow fibroblasts.
AU: Schmitz-B; Park-IA; Kaufmann-R; Thiele-J; Fischer-R
AD: Institute of Pathology, University of Cologne, Germany.
SO: Acta-Haematol. 1995; 94(4): 173-81
ISSN: 0001-5792
PY: 1995
LA: ENGLISH
CP: SWITZERLAND
AB: Interactions between stromal cells or extracellular matrix and hematopoietic cells are important factors for the very complex processes associated with differentiation and maturation in the bone marrow. To elucidate these multifold processes, the expression pattern of various adhesion molecules was studied on enriched fibroblastic populations derived from healthy volunteers. CD44 (homing cell adhesion molecule) and very late activation antigen beta 1 (VLA beta 1; CD29) could be demonstrated on almost all fibroblasts without an alteration following cytokine stimulation. On the other hand, VLA-2 (CDw49b), VLA-3 (CDw49c), VLA-4 (CDw49d), VLA-5 (CDw49e), intercellular adhesion molecule-1 (ICAM-1; CD54) and vascular cell adhesion molecule-1 (VCAM-1; CD106) were only represented by certain cell fractions. In our studies recombinant human granulocyte macrophage-colony stimulating factor failed to alter the expression pattern of these adhesion molecules, whereas recombinant human interleukin-3 (rhIL-3 showed a tendency for downregulation of the VLA antigens except for VLA beta 1. However, recombinant human transforming growth factor-beta 1 (rhTGF beta 1) exerted a reducing effect on the expression of VLA-3 and induced an increase in the VLA-5-positive fraction. In the immunoglobin class VCAM-1 revealed a decrease staining capacity after stimulation with rhTGF beta 1 and rhIL-3. Contrary to this finding, the presentation of ICAM-1 increased after administration of these mediators.
MESH: Antigens,-CD29-metabolism; Antigens,-CD44-metabolism; Bone-Marrow-metabolism; Cells,-Cultured; Immunohistochemistry-; Integrins-metabolism; Intercellular-Adhesion-Molecule-1-metabolism; Receptors,-Fibronectin-metabolism; Receptors,-Lymphocyte-Homing-metabolism
MESH: *Bone-Marrow-cytology; *Cell-Adhesion-Molecules-metabolism; *Fibroblasts-metabolism; *Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; *Interleukin-3-pharmacology; *Transforming-Growth-Factor-beta-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5; 83869-56-1
NM: collagen-receptor; integrin-alpha3beta1; integrin-alpha4beta1; Antigens,-CD29; Antigens,-CD44; Cell-Adhesion-Molecules; Integrins; Interleukin-3; Receptors,-Fibronectin; Receptors,-Lymphocyte-Homing; Transforming-Growth-Factor-beta; Intercellular-Adhesion-Molecule-1; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96190618
UD: 9608
MEDLINE EXPRESS (R) 1/96-12/96 13 of 125
TI: IL-4 and TNF-alpha induce changes in integrin expression and adhesive properties and decrease the lung-colonizing potential of HT-29 colon carcinoma cells.
AU: Herzberg-F; Schoning-M; Schirner-M; Topp-M; Thiel-E; Kreuser-ED
AD: Department of Hematology and Oncology, University Medical Center Benjamin Franklin, Free University of Berlin, Germany. herzberg@fub46.zedat.fu-berlin.de.
SO: Clin-Exp-Metastasis. 1996 Mar; 14(2): 165-75
ISSN: 0262-0898
PY: 1996
LA: ENGLISH
CP: ENGLAND
AB: The colon carcinoma cell line HT-29 was used to explore the potential of interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) to modify integrin expression and adhesive functions of tumor cells in vitro and to examine corresponding metastatic effects in vivo. Preincubation of HT-29 cells with 100 U/ml of IL-4 for 48 h downregulated the surface expression of the integrin subunits alpha 2, alpha 3, beta 1 and beta 4 after 48 h, whereas the alpha 1 subunit was upregulated. In contrast, 100 U/ml to TNF-alpha selectively upmodulated the expression of alpha v. Attachment to fibronectin of cells treated with IL-4 increased twofold (63.5% vs 32.4%). Adhesion to fibronectin (54.0% vs 32.4%) and vitronectin (37.9% vs 16.4%) was elevated in the case of TNF-alpha stimulation. Using an experimental metastasis model, HT-29 cells showed a significant reduction of their lung-colonizing potential in nude mice when preincubated with IL-4 for 48 h before intravenous injection. The decrease also observed for TNF-alpha-treated cells was less pronounced. The data indicate that the cytokines IL-4 and TNF-alpha can act as direct regulators of adhesive mechanisms of tumor cells bearing adequate receptors, thus influencing lung-colony formation.
MESH: Cell-Adhesion-drug-effects; Cell-Division-drug-effects; Fibronectins-metabolism; Gene-Expression; Integrins-genetics; Lung-Neoplasms-secondary; Mice-; Mice,-Nude; RNA,-Messenger-genetics; RNA,-Neoplasm-genetics
MESH: *Carcinoma-pathology; *Colonic-Neoplasms-pathology; *Integrins-metabolism; *Interleukin-4-pharmacology; *Tumor-Necrosis-Factor-pharmacology
TG: Animal; Female; Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0
NM: Fibronectins; Integrins; Interleukin-4; RNA,-Messenger; RNA,-Neoplasm; Tumor-Necrosis-Factor
AN: 96190825
UD: 9607
MEDLINE EXPRESS (R) 1/96-12/96 14 of 125
TI: Role of Rho in chemoattractant-activated leukocyte adhesion through integrins.
AU: Laudanna-C; Campbell-JJ; Butcher-EC
AD: Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University, CA 94305, USA.
SO: Science. 1996 Feb 16; 271(5251): 981-3
ISSN: 0036-8075
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Heterotrimeric guanine nucleotide binding protein (G protein)-linked receptors of the chemoattractant subfamily can trigger adhesion through leukocyte integrins, and in this role they are thought to regulate immune cell-cell interactions and trafficking. In lymphoid cells transfected with formyl peptide or interleukin-8 receptors, agonist stimulation activated nucleotide exchange on the small guanosine triphosphate-binding protein RhoA in seconds. Inactivation of Rho by C3 transferase exoenzyme blocked agonist-induced lymphocyte alpha4beta1 adhesion to vascular cell adhesion molecule-1 and neutrophil beta2 integrin adhesion to fibrinogen. These findings suggest that Rho participates in signaling from chemoattractant receptors to trigger rapid adhesion in leukocytes.
MESH: Amino-Acid-Sequence; Antigens,-CD-genetics; Cells,-Cultured; G-Proteins-metabolism; Guanosine-Diphosphate-metabolism; Guanosine-5'-O-3-Thiotriphosphate-metabolism; Interleukin-8-pharmacology; Mice-; Molecular-Sequence-Data; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology; Receptors,-Immunologic-genetics; Receptors,-Interleukin-genetics; Receptors,-Peptide-genetics; Signal-Transduction; Tetradecanoylphorbol-Acetate-pharmacology; Transfection-
MESH: *B-Lymphocytes-physiology; *Cell-Adhesion; *Chemotactic-Factors-pharmacology; *G-Proteins-physiology; *Integrins-physiology; *Receptors,-Lymphocyte-Homing-physiology; *Vascular-Cell-Adhesion-Molecule-1-physiology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 5T32CA09302CANCI; 1F32AI08930AINIAID
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 146-91-8; 16561-29-8; 37589-80-3; 59880-97-6
NM: chemotactic-peptide-receptor; integrin-alpha4beta1; interleukin-8-receptor; rhoA-p21-protein; Antigens,-CD; Chemotactic-Factors; G-Proteins; Integrins; Interleukin-8; Receptors,-Immunologic; Receptors,-Interleukin; Receptors,-Lymphocyte-Homing; Receptors,-Peptide; Vascular-Cell-Adhesion-Molecule-1; Guanosine-Diphosphate; Tetradecanoylphorbol-Acetate; Guanosine-5'-O-(3-Thiotriphosphate); N-Formylmethionine-Leucyl-Phenylalanine
AN: 96172356
UD: 9605
MEDLINE EXPRESS (R) 1/96-12/96 15 of 125
TI: Isolation and characterization of cell lines with genetically distinct mutations downstream of protein kinase C that result in defective activation-dependent regulation of T cell integrin function.
AU: Mobley-JL; Ennis-E; Shimizu-Y
AD: Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
SO: J-Immunol. 1996 Feb 1; 156(3): 948-56
ISSN: 0022-1767
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: beta 1-integrins expressed on resting T cells support only minimal adhesion to integrin ligands. T cell activation through multiple stimuli, including phorbol ester treatment and Ab cross-linking of the CD3/TCR complex, results in a rapid and transient switch in integrin function from low to high avidity binding. The exact nature of the intracellular signals involved in this avidity switch remain poorly defined, but the ability of phorbol esters to induce such up-regulation implicates a role for protein kinase C (PKC). We have used a genetic approach to identify factors other than PKC that regulate activation-dependent beta 1-integrin function on T cells. We isolated mutants of the Jurkat T cell line that express beta 1- and beta 2-integrins but do not exhibit increased integrin activity in response to PMA stimulation or CD3 cross-linking. PKC activity appears to be normal in the mutants. One mutation is associated with an altered form of the mitogen-activated protein kinase ERK1 and an inability to produce IL-2. Another mutant with defective integrin function has IL-2 production intact. Complementation analysis verified that these two types of mutants are genetically distinct. Thus, two mutations downstream of PKC have been identified that alter the process of integrin regulation without affecting T cell viability or proliferative capacity. These mutants represent novel reagents for the identification of integrin regulatory factors and indicate possible sites of pharmacologic intervention that could prevent integrin-dependent migration and localization in the process of inflammation, while leaving other T cell functions intact.
MESH: Antigens,-CD18-genetics; Antigens,-CD29-genetics; Cell-Adhesion-genetics; Cell-Separation; Gene-Expression-Regulation,-Neoplastic-immunology; Genetic-Complementation-Test; Integrins-biosynthesis; Integrins-physiology; Interleukin-2-biosynthesis; Interleukin-2-genetics; Lymphoma,-T-Cell-genetics; Protein-Kinase-C-deficiency; Protein-Kinase-C-physiology; Protein-Kinases-genetics; Tumor-Cells,-Cultured
MESH: *Gene-Expression-Regulation,-Neoplastic; *Integrins-genetics; *Lymphocyte-Transformation-genetics; *Lymphoma,-T-Cell-enzymology; *Mutation-; *Protein-Kinase-C-genetics
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI31126AINIAID
RN: EC 2.7.1.-; EC 2.7.1.37; 0; 0; 0; 0
NM: Protein-Kinase-C; Protein-Kinases; Antigens,-CD18; Antigens,-CD29; Integrins; Interleukin-2
AN: 96144313
UD: 9605
SB: AIM
MEDLINE EXPRESS (R) 1/96-12/96 16 of 125
TI: Lymphocyte adhesion and transendothelial migration in the central nervous system: the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. off
AU: Greenwood-J; Wang-Y; Calder-VL
AD: Department of Clinical Ophthalmology, University College London, UK.
SO: Immunology. 1995 Nov; 86(3): 408-15
ISSN: 0019-2805
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: Lymphocyte adhesion to and migration across endothelial cell (EC) monolayers, derived from the rat blood-retinal barrier (BRB), were measured in vitro. The binding of concanavalin A (Con A)-activated peripheral lymph node lymphocytes and the migration of CD4+ T-cell lines could be significantly increased by treating the EC with interleukin-1 beta (IL-1 beta). To determine the role of various adhesion molecules during the processes of lymphocyte binding and transmonolayer migration (diapedesis), lymphocytes were treated with monoclonal antibody (mAb) specific for CD11a (alpha L subunit of leucocyte functional antigen-1; LFA-1), CD18 (beta 2 subunit of leucam family) and CD49d (alpha 4 subunit of very late activation antigen-4; VLA-4) and EC with mAb specific for CD54 (intercellular adhesion molecule-1; ICAM-1) and CD106 (vascular cell adhesion molecule-1; VCAM-1). Binding of the highly adhesive but non-migratory Con A-activated lymphocytes was inhibited by mAb to CD11a (reduced to 73% and 65% of control lymphocyte adhesion) and CD18 (42% and 54%) on non-activated and IL-1 beta-treated EC, respectively, but not by mAb to ICAM-1 or VCAM-1. Diapedesis of the highly migratory T-cell line lymphocytes was also blocked by antibodies to CD11a (reduced to 11% and 10% of control T-cell migration), CD18 (29% and 43%) but in addition was also inhibited by anti-ICAM-1 (17% and 53%) on non-activated and IL-1 beta treated EC, respectively. Both anti-VLA-4 and anti-VCAM-1 were also effective in producing a smaller reduction in migration, but only on IL-1 beta activated EC (66% and 58% of control migration, respectively). These studies indicate that lymphocyte adhesion to central nervous system (CNS) vascular EC is largely dependent on LFA-1 but not through its interaction with ICAM-1. In contrast, lymphocyte diapedesis is mostly supported through the LFA-1/ICAM-1 pairing, with a small proportion being mediated by VLA-4/VCAM-1 on IL-1 beta-activated EC. This latter pathway, however, also appears to be dependent on LFA-1 interacting with the EC.
MESH: Antibodies,-Blocking-pharmacology; Cell-Adhesion-physiology; Cell-Movement-physiology; Endothelium-cytology; Flow-Cytometry; Immunologic-Techniques; Integrins-physiology; Intercellular-Adhesion-Molecule-1-physiology; Lymphocyte-Function-Associated-Antigen-1-physiology; Rats-; Rats,-Inbred-Strains; Receptors,-Lymphocyte-Homing-physiology; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Blood-Retinal-Barrier-physiology; *Cell-Adhesion-Molecules-physiology; *Lymphocytes-physiology
TG: Animal; Female
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antibodies,-Blocking; Cell-Adhesion-Molecules; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96148607
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 17 of 125
TI: Human intestinal intraepithelial lymphocytes bind to mucosal mesenchymal cells through VLA4 and CD11A.
AU: Ebert-EC; Roberts-AI
AD: Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA.
SO: Cell-Immunol. 1996 Jan 10; 167(1): 108-14
ISSN: 0008-8749
PY: 1996
LA: ENGLISH
CP: UNITED-STATES
AB: Human intestinal intraepithelial lymphocytes (IEL), predominantly CD8+ T lymphocytes, are uniquely situated at the basolateral surfaces of epithelial cells in contact with the myofibroblasts that comprise the basement membrane. Since mesenchymal cells may anchor IEL in this location and may also serve as antigen-presenting cells, the mechanism of binding to IEL was investigated. Lymphocytes were radiolabeled with [51Cr] sodium chromate, cocultured with mesenchymal cell monolayers, and the nonadherent lymphocytes removed by washes. Those adherent to the monolayers were counted by measuring the amount of radiolabel retained in the well. A large fraction of IL-2-activated IEL bound to KD (lip fibroblast), HISM (jejunal smooth muscle), and JF (jejunal fibroblast) cell lines after a 2-hr incubation: 33 +/- 11, 37 +/-14, and 48 +/- 15%, respectively. When monoclonal antibodies directed at the alpha chains of the very late activation antigens (CD49) were added alone or combined with anti CD11a to assays measuring IEL binding to KD or JF monolayers, the greatest inhibition (33 to 38%) occurred with anti-alpha 4 combined with anti-CD11a. The majority of IEL expressed alpha 1 and alpha 4 before and after a 3-day culture with IL-2, with no change in surface density. VCAM-1, a binding partner to alpha 4, was not expressed on KD or JF cells, and anti-VCAM antibody had no effect on binding. In summary, alpha 4 and CD11a on IEL mediate binding to mesenchymal cells.
MESH: Cell-Adhesion; Cell-Line; Interleukin-2-pharmacology; Intestinal-Mucosa-immunology; Lymphocyte-Transformation; Vascular-Cell-Adhesion-Molecule-1-physiology
MESH: *Integrins-physiology; *Intestinal-Mucosa-cytology; *Lymphocyte-Function-Associated-Antigen-1-physiology; *Lymphocytes-physiology; *Receptors,-Lymphocyte-Homing-physiology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: DK42166DKNIDDK
RN: 0; 0; 0; 0; 0; 0
NM: integrin-alpha4beta1; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Vascular-Cell-Adhesion-Molecule-1
AN: 96139357
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 18 of 125
TI: VLA-6 (CDw49f) is an important adhesion molecule in NK cell-mediated cytotoxicity following autologous or allogeneic bone marrow transplantation.
AU: Lowdell-MW; Shamim-F; Hamon-M; Macdonald-ID; Prentice-HG
AD: Department of Haematology, Royal Free Hospital School of Medicine, London, UK.
SO: Exp-Hematol. 1995 Dec; 23(14): 1530-4
ISSN: 0301-472X
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Graft-vs.-leukemia (GVL) is postulated to be the principal mechanism responsible for continued remission after allogeneic bone marrow transplantation (BMT). The specific cytotoxic effectors mediating this effect are as yet undefined, but the major histocompatibility complex (MHC)-nonrestricted lysis of tumor cell lines by natural killer (NK) and lymphokine-activated killer (LAK) cells from recipients of allogeneic BMTs has been proposed as an in vitro correlate of GVL. In vitro culture or treatment in vivo with interleukin-2 (IL-2) is associated with enhanced NK cytotoxicity and lysis of NK-resistant targets (LAK cytotoxicity). NK, LAK, and cytotoxic T lymphocytes (CTL) have cytotoxic properties against autologous and allogeneic leukemic targets. These immune effector cells require receptor-ligand interaction for target recognition and adhesion via specific molecules such as integrins, a group of heterodimeric transmembrane glycoproteins. The integrins include the very late activation (VLA) subfamily, which all share the same beta 1 subunit but have distinct chains. VLA-6 (CDw49f) has been identified on NK cells and binds to laminin, a basement membrane protein found on malignant tumor cells but not normal cells. Monoclonal antibodies (mAbs) to laminin have been found to inhibit in vitro cytotoxicity of the tumor cell line K562, suggesting an important role for VLA-6 in this interaction. The specific aim of this study was to investigate the role of VLA-6 in the interactions of the tumor cell lines K562 and Daudi with peripheral blood lymphocytes (PBL) acting as effectors in cell-mediated cytotoxicity from normal volunteers, patients recovering from chemotherapy, and patients recovering from autologous or allogeneic BMT. In over 96% of assays, incubation of effector cells with anti-CDw49f mAbs led to detectable inhibition of NK and LAK cell-mediated cytotoxicity. More notably, the degree of anti-VLA6-induced suppression of LAK activity was significantly greater in the normal donors than in any of the patient groups, despite a significantly lower incidence of expression of VLA-6 on NK cells from controls than from patients. This implies a reduced role for this adhesion molecule in LAK activity following some form of in vivo stimulation. This hypothesis is supported by the observation that addition of exogenous IL-2 to the cultures ameliorated the effect of VLA-6 blockade, although the incidence and level of VLA-6 expression was unchanged by IL-2. In contrast, VLA-6 blocking led to a greater reduction in NK activity of BMT recipients than of normal donors, demonstrating that the VLA-6 adhesion pathway is important in this group of patients. These results indicate that the VLA-6-laminin interaction is important in normal NK-target interaction but may play a less significant role in the innate cytotoxic response post-BMT, perhaps reflecting subtle differences in the subsets of NK cells present in BMT recipients compared with normal donors.
MESH: Antibodies,-Monoclonal-pharmacology; Flow-Cytometry; Fluorescent-Antibody-Technique; Graft-vs-Host-Reaction; Killer-Cells,-Lymphokine-Activated-immunology; Laminin-immunology; Laminin-metabolism; Leukemia-therapy; Lymphocytes-immunology; Transplantation,-Autologous; Transplantation,-Homologous; Tumor-Cells,-Cultured
MESH: *Bone-Marrow-Transplantation-immunology; *Cytotoxicity,-Immunologic; *Integrins-immunology; *Killer-Cells,-Natural-immunology; *Leukemia-immunology; *Receptors,-Laminin-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0
NM: integrin-alpha6beta1; Antibodies,-Monoclonal; Integrins; Laminin; Receptors,-Laminin
AN: 96130286
UD: 9604
MEDLINE EXPRESS (R) 1/96-12/96 19 of 125
TI: Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands protects CD4+ allergen-specific T-cell clones from programmed cell death.
AU: Agea-E; Bistoni-O; Bini-P; Migliorati-G; Nicoletti-I; Bassotti-G; Riccardi-C; Bertotto-A; Spinozzi-F
AD: Department of Internal Medicine, University of Perugia, Italy.
SO: Allergy. 1995 Aug; 50(8): 677-82
ISSN: 0105-4538
PY: 1995
LA: ENGLISH
CP: DENMARK
AB: An optimal stimulation of CD4+ cells in an immune response requires not only signals transduced via the TcR/CD3 complex, but also costimulatory signals delivered as a consequence of interactions between T-cell surface-associated costimulatory receptors and their counterparts on antigen-presenting cells (APC). The intercellular adhesion molecule-1 (ICAM-1, CD54) efficiently costimulates proliferation of resting, but not antigen-specific, T cells. In contrast, CD28 and CD2 support interleukin (IL)-2 synthesis and proliferation of antigen-specific T cells more efficiently than those of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. Cypress-specific T-cell clones (TCC) were generated from four allergic subjects during in vivo seasonal exposure to the allergen. Purified cypress extract was produced directly from fresh collected pollen and incubated with the patients' mononuclear cells. Repeated allergen stimulation was performed in T-cell cultures supplemented with purified extract and autologous APC. The limiting-dilution technique was then adopted to generate allergen-specific TCC, which were also characterized by their cytokine secretion pattern as Th0 (IL-4 plus interferon-gamma) or Th2 (IL-4). Costimulation-induced proliferation or apoptosis was measured by propidium iodide cytofluorometric assay. By cross-linking cypress-specific CD4+ and CD8+ T-cell clones with either anti-CD3 or anti-CD2, anti-CD28, and anti-CD54 monoclonal antibodies, we demonstrated that CD4+ clones (with Th0- or Th2-type cytokine production pattern) undergo programmed cell death only after anti-CD3 stimulation, whereas costimulation with either anti-CD54 or anti-CD28 protects target cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Antigen-Presenting-Cells-immunology; Antigens,-CD2-immunology; Antigens,-CD28-immunology; Cell-Division; Cells,-Cultured; Clone-Cells; Hay-Fever-immunology; Intercellular-Adhesion-Molecule-1-immunology; Interleukin-1-metabolism; Pollen-immunology
MESH: *Allergens-immunology; *Antigens,-CD3-immunology; *Apoptosis-physiology; *CD4-Positive-T-Lymphocytes-immunology; *CD8-Positive-T-Lymphocytes-immunology; *Integrins-immunology; *Receptors,-Antigen,-T-Cell-immunology
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Allergens; Antigens,-CD2; Antigens,-CD28; Antigens,-CD3; Integrins; Interleukin-1; Receptors,-Antigen,-T-Cell; Intercellular-Adhesion-Molecule-1
AN: 96098155
UD: 9603
MEDLINE EXPRESS (R) 1/96-12/96 20 of 125
TI: VLA-4/VCAM-1 pathway in human periodontal disease.
AU: Tsurumachi-T; Nishi-K; Hayashi-M; Saito-T; Saito-I; Moro-I
AD: Department of Endodontics, Nihon University School of Dentistry, Tokyo, Japan.
SO: Adv-Exp-Med-Biol. 1995; 371B: 1131-3
ISSN: 0065-2598
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
MESH: E-Selectin-genetics; Gene-Expression; Intercellular-Adhesion-Molecule-1-genetics; Interleukin-1-pharmacology; Kinetics-; Periapical-Periodontitis-genetics; Polymerase-Chain-Reaction; RNA,-Messenger-biosynthesis; RNA,-Messenger-genetics
MESH: *Integrins-genetics; *Periapical-Periodontitis-immunology; *Receptors,-Lymphocyte-Homing-genetics; *Vascular-Cell-Adhesion-Molecule-1-genetics
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; E-Selectin; Integrins; Interleukin-1; Receptors,-Lymphocyte-Homing; RNA,-Messenger; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 96001706
UD: 9603
MEDLINE EXPRESS (R) 1/96-12/96 21 of 125
TI: Presence of T cells with activated and memory phenotypes in inflammatory spinal cord lesions.
AU: Barten-DM; Clark-RB; Ruddle-NH
AD: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.
SO: J-Immunol. 1995 Dec 1; 155(11): 5409-18
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The phenotypic and functional characteristics of activated T cells and recruited unactivated T cells at an inflammatory site were examined using a V beta 4+ myelin basic protein-specific T cell clone in a passively transferred model of experimental allergic encephalomyelitis. A high percentage of the T cells isolated from the central nervous system (CNS) were V beta 4+. This population exhibited the characteristics of activated T cells based on the proportion of cells in the blast state, their ability to proliferate in response to IL-2 or CNS Ag, and their expression of activation/memory cell markers. Activated V beta 4+ T cells were also observed in the periphery. Large numbers of V beta 4- T cells, which are entirely host-recruited, were also found in the CNS, where they demonstrated the properties of memory cells. There were differences in adhesion molecule expression between CNS V beta 4+ T cells and peripheral V beta 4+ T cells, although both populations were in activated state. V beta 4+ T cells at the site of Ag expression (the spinal cord) demonstrated higher levels of LFA-1 and CD44, but lower levels of VLA-4 and intercellular adhesion molecule-1, than did V beta 4+ T cells in the spleen. In contrast, the levels of all of these adhesion molecules on recruited V beta 4- T cells were higher in the CNS than in the periphery. This experimental model allows the detailed characterization of different T cell populations isolated from the same inflammatory site.
MESH: Antigens,-CD44-biosynthesis; Cells,-Cultured; Encephalomyelitis,-Allergic-etiology; Encephalomyelitis,-Allergic-pathology; Immunization,-Passive; Integrins-biosynthesis; Intercellular-Adhesion-Molecule-1-biosynthesis; Interleukin-2-immunology; Lymphocyte-Function-Associated-Antigen-1-biosynthesis; Lymphocyte-Transformation-immunology; Mice-; Mice,-Inbred-Strains; Myelin-Basic-Proteins-immunology; Receptors,-Antigen,-T-Cell,-alpha-beta-biosynthesis; Receptors,-Antigen,-T-Cell,-alpha-beta-immunology; Receptors,-Interleukin-2-biosynthesis; Receptors,-Lymphocyte-Homing-biosynthesis; Spinal-Cord-immunology; Spleen-cytology
MESH: *Encephalomyelitis,-Allergic-immunology; *Immunologic-Memory-immunology; *Lymphocyte-Transformation; *Spinal-Cord-pathology; *T-Lymphocytes-immunology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: 1F32NS09078NSNINDS
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antigens,-CD44; Integrins; Interleukin-2; Lymphocyte-Function-Associated-Antigen-1; Myelin-Basic-Proteins; Receptors,-Antigen,-T-Cell,-alpha-beta; Receptors,-Interleukin-2; Receptors,-Lymphocyte-Homing; Intercellular-Adhesion-Molecule-1
AN: 96072821
UD: 9602
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 22 of 125
TI: Signal transduction through chondrocyte integrin receptors induces matrix metalloproteinase synthesis and synergizes with interleukin-1.
AU: Arner-EC; Tortorella-MD
AD: Du Pont Merck Pharmaceutical Company, Wilmington, DE 19880-0400, USA.
SO: Arthritis-Rheum. 1995 Sep; 38(9): 1304-14
ISSN: 0004-3591
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE. To study the role of signal transduction via integrin receptors in the production of metalloproteinase by rabbit articular chondrocytes. METHODS. Confluent, primary rabbit articular chondrocytes (RAC) were incubated for 72 hours in the presence of interleukin-1 (IL-1), Arg-Gly-Asp (RGD) peptide, or a combination of IL-1 and RGD peptide. Media were analyzed for stromelysin enzymatic activity using a 3H-labeled transferrin substrate, and for stromelysin and collagenase protein by Western analysis. Gelatinase activity was analyzed by gelatin zymography. IL-1 receptor antagonist (IL-1Ra) protein was used to determine the involvement of IL-1 in mediating the effects of RGD peptide, and fluorescence-activated cell sorter analysis (FACS) was used to examine the effect of IL-1 on chondrocyte integrin subunit expression. RESULTS. RGD peptides induced chondrocyte synthesis of stromelysin, collagenase, and 92-kd gelatinase B, and increased synthesis of the constitutively expressed 72-kd gelatinase A. Further studies focusing on stromelysin demonstrated that this up-regulation was concentration dependent and that RGD peptides synergized with IL-1 in inducing stromelysin synthesis. RGD-induced stromelysin production was inhibited by the IL-1Ra in a concentration-dependent manner, indicating that induction by RGD requires binding of IL-1 to its receptor. FACS analysis of RAC showed that IL-1 stimulation increased the expression of beta 1 and alpha v integrin subunits on the chondrocyte surface. CONCLUSION. Our data demonstrate that signal transduction through chondrocyte integrin receptors up-regulates metalloproteinase expression and that this is likely mediated through induction of IL-1. They also suggest that the binding of adhesion molecules to their chondrocyte integrin receptors reduces the amount of IL-1 required to induce stromelysin synthesis. Up-regulation of chondrocyte integrin expression by IL-1 may play a role in the synergistic effects seen with a combination of IL-1 and RGD peptides. Since elevated levels of both IL-1 and adhesion molecules are present in rheumatoid arthritis and osteoarthritis synovial fluid, our data suggest that this interaction may be important in mediating the cartilage destruction accompanying these diseases.
MESH: Cartilage-cytology; Cells,-Cultured; Drug-Synergism; Enzyme-Induction; Fibronectins-pharmacology; Interleukin-1-pharmacology; Oligopeptides-pharmacology; Peptide-Fragments-pharmacology; Rabbits-; Receptors,-Interleukin-1-antagonists-and-inhibitors
MESH: *Cartilage-metabolism; *Extracellular-Matrix-metabolism; *Integrins-physiology; *Interleukin-1-metabolism; *Metalloproteinases-metabolism; *Signal-Transduction
TG: Animal; Male
PT: JOURNAL-ARTICLE
RN: EC 3.4.24; 0; 0; 0; 0; 0; 0; 99896-85-2
NM: Metalloproteinases; Fibronectins; Integrins; Interleukin-1; Oligopeptides; Peptide-Fragments; Receptors,-Interleukin-1; arginyl-glycyl-aspartic-acid
AN: 96016062
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 23 of 125
TI: Effect of interleukin-5 and granulocyte-macrophage colony stimulating factor on in vitro eosinophil function: comparison with airway eosinophils.
AU: Sedgwick-JB; Quan-SF; Calhoun-WJ; Busse-WW
AD: Department of Medicine, University of Wisconsin, Madison, USA.
SO: J-Allergy-Clin-Immunol. 1995 Sep; 96(3): 375-85
ISSN: 0091-6749
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Eosinophils are hypothesized to be crucial in the development of allergic airway inflammation; however, the actual mechanisms that determine their inflammatory activity are still largely undefined. To investigate the factors that regulate eosinophil function in allergic airway disease, we have previously used segmental bronchoprovocation with allergen to study ex vivo eosinophil function. To determine whether the functional changes associated with airway eosinophils obtained by bronchoalveolar lavage 48 hours after antigen challenge are caused by exposure to airway-generated cytokines, normodense blood eosinophils were cultured in vitro with recombinant human interleukin-5 (IL-5) or granulocyte-macrophage colony stimulating factor (GM-CSF). The effect of cytokine exposure was then evaluated on selected cell functions. In vitro incubation with these cytokines for 24 hours significantly increased eosinophil membrane expression of CD18 and CD11b compared with culture in medium alone or eosinophils obtained by bronchoalveolar lavage. N-formyl-methionyl-leucyl-phenylalanine-stimulated superoxide anion generation was slightly but significantly enhanced by incubation with IL-5 but not with GM-CSF. In addition, spontaneous adhesion to human umbilical vein endothelial cell monolayers was increased after exposure to both IL-5 and GM-CSF. However, activated adhesion was enhanced only by culture with IL-5 and stimulation with N-formyl-methionyl-leucyl-phenylalanine. The magnitude of functional changes after in vitro preincubation of eosinophils with these cytokines did not achieve levels of superoxide anion and adhesion noted with airway eosinophils obtained after segmental bronchoprovocation with allergen. These observations raise the possibility that the contribution of IL-5 and GM-CSF to phenotypic changes of airway eosinophils is principally to enhance survival and expression of adhesion proteins. These data also suggest that, in addition to the generation of proinflammatory cytokines, other factors contribute to phenotypic changes in eosinophils as they migrate from the blood to the airway.
MESH: Blood-Cells-drug-effects; Blood-Cells-physiology; Bronchoalveolar-Lavage-Fluid-cytology; Cell-Adhesion-drug-effects; Cell-Survival-drug-effects; Cells,-Cultured; Cytokines-pharmacology; Eosinophils-physiology; Hay-Fever-pathology; Integrins-metabolism; Rhinitis,-Allergic,-Perennial-pathology; Superoxides-metabolism
MESH: *Eosinophils-drug-effects; *Granulocyte-Macrophage-Colony-Stimulating-Factor-pharmacology; *Interleukin-5-pharmacology
TG: Comparative-Study; Human; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: RO1AI23181AINIAID; RO1HL44098HLNHLBI
RN: 0; 0; 0; 11062-77-4; 83869-56-1
NM: Cytokines; Integrins; Interleukin-5; Superoxides; Granulocyte-Macrophage-Colony-Stimulating-Factor
AN: 96013053
UD: 9601
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 24 of 125
TI: T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.
AU: Langley-JG; Boros-DL
AD: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
SO: Infect-Immun. 1995 Oct; 63(10): 3980-6
ISSN: 0019-9567
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation.
MESH: Antibodies,-Monoclonal-immunology; Cytokines-biosynthesis; Granuloma-etiology; Integrins-analysis; Intercellular-Adhesion-Molecule-1-analysis; Lymphocyte-Function-Associated-Antigen-1-analysis; Mice-; Mice,-Inbred-CBA; Rats-; Receptors,-Lymphocyte-Homing-analysis
MESH: *Integrins-physiology; *Intercellular-Adhesion-Molecule-1-physiology; *Lymphocyte-Function-Associated-Antigen-1-physiology; *Receptors,-Lymphocyte-Homing-physiology; *Schistosomiasis-mansoni-immunology; *T-Lymphocytes-immunology
TG: Animal; Female; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI12913AINIAID
RN: 0; 0; 0; 0; 0; 0; 126547-89-5
NM: integrin-alpha4beta1; Antibodies,-Monoclonal; Cytokines; Integrins; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Lymphocyte-Homing; Intercellular-Adhesion-Molecule-1
AN: 96009755
UD: 9601
MEDLINE EXPRESS (R) 1991-1995 25 of 125
TI: Functional characteristics of mature granulocytes in a patient with acute promyelocytic leukemia treated with all-trans retinoic acid.
AU: Sham-RL; Phatak-PD; Belanger-KA; Braggins-C; Packman-CH
AD: Department of Medicine, Rochester General Hospital, NY 14621, USA.
SO: Leuk-Res. 1995 Aug; 19(8): 505-11
ISSN: 0145-2126
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: All-trans retinoic acid (ATRA) is a differentiating agent that has been successfully used in the treatment of patients with acute promyelocytic leukemia (APL). Functional properties of peripheral blood neutrophils from a patient with APL during treatment with ATRA have been studied. Wright stain of patient neutrophils showed hypogranulation and loose nuclear chromatin when compared with normal neutrophils. These cells were of lower density than normal neutrophils and separated on density gradient centrifugation with mononuclear cells. Surface antigen expression by FACS distinguished these cells from lymphocytes. The histograms showed a population of larger cells expressing CD18 and CD11b, distinct from the smaller cells which did not express CD11b. fMLP caused an increase in intracellular calcium (measured spectrophotometrically) that was inhibited by the calcium chelator BAPTA. Actin polymerization following cell activation was measured using NBD-phallacidin staining and FACS. Both IL-8 and fMLP caused rapid increases using F-actin content (2.5-3.0 fold), which were of greater magnitude than generally seen with normal neutrophils. Treatment with BAPTA before activation with fMLP did not blunt the actin responses, despite complete inhibition of an intracellular calcium increase. In summary, neutrophils derives from differentiated APL cells express CD18/CD11b, and exhibit a similar degree of actin polymerization in response to fMLP and IL-8, independent of an increase in intracellular calcium. Although the actin responses are greater than normal neutrophils, most properties are similar, supporting the contention that these cells can protect the host. The exaggerated actin response to inflammatory mediators, however, may play a role in the 'retinoic acid syndrome'.
MESH: Actins-metabolism; Antigens,-Surface-metabolism; Calcium-metabolism; Cell-Adhesion-Molecules-metabolism; Cell-Size-drug-effects; Granulocytes-drug-effects; Immunophenotyping-; Integrins-metabolism; Interleukin-8-pharmacology; Middle-Age; N-Formylmethionine-Leucyl-Phenylalanine-pharmacology
MESH: *Granulocytes-physiology; *Leukemia,-Promyelocytic,-Acute-drug-therapy; *Tretinoin-therapeutic-use
TG: Case-Report; Human; In-Vitro; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 126880-86-2; 302-79-4; 59880-97-6; 7440-70-2
NM: Actins; Antigens,-Surface; Cell-Adhesion-Molecules; Integrins; Interleukin-8; L-Selectin; Tretinoin; N-Formylmethionine-Leucyl-Phenylalanine; Calcium
AN: 95387636
UD: 9512
MEDLINE EXPRESS (R) 1991-1995 26 of 125
TI: Modulation of the adhesion of hemopoietic progenitor cells to the RGD site of fibronectin by interleukin 3.
AU: Hardy-CL; Minguell-JJ
AD: Department of Veterans Affairs Medical Center, Jackson, Mississippi 39216, USA.
SO: J-Cell-Physiol. 1995 Aug; 164(2): 315-23
ISSN: 0021-9541
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The integrins are a class of adhesion molecules which have been implicated in the homing of hemopoietic stem cells and in their restriction within the bone marrow. Integrins function as mediators of cell-extracellular matrix (ECM) interactions amd also of cell-cell interactions. They are unique membrane receptors which are capable of activation, change in affinity, and change in expression. Because of their broad potential for modulation we examined the effect of a cytokine growth factor which is present constitutively in the marrow, interleukin 3 (IL3), on integrin-mediated adherence of hemopoietic progenitor cells to the matrix component fibronectin (FN). The multipotential murine cell line B6Sut and the committed granulocyte progenitor cell line FDCP-1 were used. Both of these cell lines have been shown to bind to FN-coated dishes and to dishes coated with the 120 kDa and 40 kDa chymotryptic fragments of FN. It was found that after a brief withdrawal of IL3 the cells lost 80% adherence to the 120 kDa FN fragment containing the RGD cell binding site. This loss of binding was not related to a loss of viability, appeared unrelated to the growth/survival activity of IL3, and was quickly reversible by readdition of the growth factor. Adhesion of these cells to the RGD site was likely mediated by alpha 5 beta 1 integrin which was identified in the cell membrane of both cell lines, but present in low copy number in B6Sut cells. Two antibodies against the external and internal domains of alpha 5 and one antibody against beta 1 were used to study expression of the integrin. By flow cytometry the expression of alpha 5 was found to decrease in both cell lines by 4 h in the absence of IL3. The relative mean fluorescence intensity for B6Sut cells decreased from 1.0 (control cells always in the presence of IL3) to 0.6 over 4 h, and for FDCP-1 cells the decrement was from 1.0 to 0.8. The loss of RGD-mediated adhesion in the absence of IL3 appeared to proceed through this decrement in expression of the integrin; a loss of affinity of the receptor for its substrate was not detected. The general modulation of integrin activity by growth factors is of great interest because of its potential negative impact on the endothelium in cytokine-treated patients, and also because of its potential positive impact on engraftment during clinical bone marrow transplantation.
MESH: Cell-Adhesion-drug-effects; Cell-Line; Chymotrypsin-; Dose-Response-Relationship,-Drug; Hematopoietic-Stem-Cells-drug-effects; Integrins-metabolism; Kinetics-; Mice-; Oligopeptides-pharmacology; Peptide-Fragments-physiology; Receptors,-Fibronectin-metabolism
MESH: *Fibronectins-physiology; *Hematopoietic-Stem-Cells-physiology; *Interleukin-3-pharmacology; *Oligopeptides-physiology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 3.4.21.1; 0; 0; 0; 0; 0; 0; 96426-21-0; 99896-85-2
NM: Chymotrypsin; Fibronectins; Integrins; Interleukin-3; Oligopeptides; Peptide-Fragments; Receptors,-Fibronectin; glycyl-arginyl-glycyl-aspartyl-serine; arginyl-glycyl-aspartic-acid
AN: 95348206
UD: 9511
MEDLINE EXPRESS (R) 1991-1995 27 of 125
TI: Expression and functional significance of an activation-dependent epitope of the beta 1 integrins in chronic inflammatory diseases.
AU: Arroyo-AG; Garcia-Vicuna-R; Marazuela-M; Yednock-TA; Gonzalez-Amaro-R; Sanchez-Madrid-F
AD: Servicio de Inmunologia, Hospital de la Princesa, Universidad Autonoma, Madrid, Spain.
SO: Eur-J-Immunol. 1995 Jun; 25(6): 1720-8
ISSN: 0014-2980
PY: 1995
LA: ENGLISH
CP: GERMANY
AB: The avidity of VLA integrins for their ligands can be increased by their transition to an active conformational state. This conformational change can be detected with a novel monoclonal antibody (mAb), termed 15/7, that recognizes an activation-dependent conformational epitope on the common beta 1 polypeptide of different VLA alpha beta 1 integrins. In an attempt to understand the possible role of the active conformational state of beta 1 integrins in vivo, we first investigated the expression of 15/7 epitope on T lymphocytes from patients with chronic inflammatory joint diseases. An enhanced expression of the 15/7 epitope was found in the synovial fluid (SF) T lymphocytes from these patients as compared to their peripheral blood (PB) T cells. The effect of different cytokines on the appearance of the 15/7 activation epitope in PB T lymphocytes was subsequently analyzed; interferon-gamma, interleukin-2 and, to a lower extent, tumor necrosis factor-alpha were able to induce an increased expression of the 15/7 epitope. This enhanced 15/7 expression correlated with a higher binding ability to fibronectin of cytokine-activated T cells. The presence of this activation epitope was detected in a small proportion of T lymphocytes scattered within inflammatory foci of synovial membrane from rheumatoid arthritis and thyroid glands from Hashimoto's chronic thyroiditis. We then analyzed the possible role of 15/7 epitope expression on cell adhesion in vitro. Immunofluorescence studies showed that the 15/7 epitope displayed a spot-like distribution, selectively decorating adhesive contacts of U-937 myelomonocytic cells attached to the 80 kDa proteolytic fragment of fibronectin (FN80). Furthermore, the anti-beta 1 15/7 mAb was able to induce both T lymphocyte, Jurkat and U-937 cellular binding and spreading on FN80. Altogether these results indicate that an activated conformation of beta 1 integrins is detected in vivo in lymphocyte infiltrates from chronic inflammatory conditions. The active conformations of beta 1 integrins are regulated by physiologic mediators such as cytokines, play an important role in cellular attachment and spreading, and appear to be involved in the development of inflammatory processes.
MESH: Arthritis,-Rheumatoid-pathology; Cytokines-metabolism; Cytokines-pharmacology; Epitopes-immunology; Immunohistochemistry-; Integrins-chemistry; Integrins-immunology; Organ-Specificity; T-Lymphocytes-metabolism
MESH: *Arthritis,-Rheumatoid-immunology; *Integrins-biosynthesis; *T-Lymphocytes-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: Antigens,-CD29; Cytokines; Epitopes; Integrins
AN: 95339889
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 28 of 125
TI: Interaction of mast cells with extracellular matrix proteins.
AU: Metcalfe-DD
AD: Allergic Diseases Section, NIAID/NIH, Bethesda, MD 20892, USA.
SO: Int-Arch-Allergy-Immunol. 1995 May-Jun; 107(1-3): 60-2
ISSN: 1018-2438
PY: 1995
LA: ENGLISH
CP: SWITZERLAND
AB: It is possible to divide surface receptors on mast cells conceptually into three groups. The first consists of immune response receptors. The index receptor for this group is Fc epsilon RI, now joined by Fc gamma receptors and receptors for complement products. The second group of receptors are those that are involved in growth and differentiation, such as those for interleukin-3 and stem cell factor. The third group consists of receptors regulating mast cell trafficking and distribution. Principle among the latter group of receptors are those that engage extracellular matrix components, including the classical integrin receptors. The engagement of mast cells to matrix components not only has relevance in determining the tissue distribution of mast cells, but also appears to have a major influence on the biologic responsiveness of mast cells to immune- and growth-factor-receptor-mediated signals.
MESH: Amino-Acid-Sequence; Cell-Adhesion-drug-effects; Hematopoietic-Cell-Growth-Factors-pharmacology; Mast-Cells-drug-effects; Mice-; Molecular-Sequence-Data; Rats-; Receptors,-IgE-metabolism
MESH: *Extracellular-Matrix-Proteins-metabolism; *Integrins-metabolism; *Mast-Cells-metabolism
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 0; 0; 0
NM: Extracellular-Matrix-Proteins; Hematopoietic-Cell-Growth-Factors; Integrins; Receptors,-IgE; Stem-Cell-Factor
AN: 95337849
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 29 of 125
TI: Integrin-mediated tyrosine phosphorylation and cytokine message induction in monocytic cells. A possible signaling role for the Syk tyrosine kinase.
AU: Lin-TH; Rosales-C; Mondal-K; Bolen-JB; Haskill-S; Juliano-RL
AD: Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill 27599, USA.
SO: J-Biol-Chem. 1995 Jul 7; 270(27): 16189-97
ISSN: 0021-9258
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Activation of cytoplasmic tyrosine kinases is an important aspect of signal transduction mediated by integrins. In the human monocytic cell line THP-1, either integrin-dependent cell adhesion to fibronectin or ligation of beta 1 integrins with antibodies causes a rapid and intense tyrosine phosphorylation of two sets of proteins of about 65-75 and 120-125 kDa. In addition, integrin ligation leads to nuclear translocation of the p50 and p65 subunits of the NF-kappa B transcription factor, to activation of a reporter gene driven by a promoter containing NF-kappa B sites, and to increased levels of mRNAs for immediate-early genes, including the cytokine interleukin (IL)-1 beta. The tyrosine kinase inhibitors genistein and herbimycin A block both integrin-mediated tyrosine phosphorylation and increases in IL-1 beta message levels, indicating a causal relationship between the two events. The components tyrosine phosphorylated subsequent to cell adhesion include paxillin, pp125FAK, and the SH2 domain containing tyrosine kinase Syk. In contrast, integrin ligation with antibodies induces tyrosine phosphorylation of Syk but not of FAK or paxillin. In adhering cells, pre-treatment with cytochalasin D suppresses tyrosine phosphorylation of FAK and paxillin but not of Syk, while IL-1 beta message induction is unaffected. These observations indicate that the Syk tyrosine kinase may be an important component of an integrin signaling pathway in monocytic cells, leading to activation of NF-kappa B and to increased levels of cytokine messages.
MESH: Cell-Adhesion-physiology; Cell-Adhesion-Molecules-metabolism; Enzyme-Activation; Enzyme-Precursors-antagonists-and-inhibitors; Extracellular-Matrix-Proteins-metabolism; Fibronectins-metabolism; Gene-Expression-Regulation,-Neoplastic; Genes,-Reporter; Inflammation-; Interleukin-1-genetics; Isoflavones-pharmacology; Leukemia,-Monocytic,-Acute; NF-kappa-B-metabolism; Phosphorylation-; Protein-Tyrosine-Kinase-antagonists-and-inhibitors; Quinones-pharmacology; RNA,-Messenger-biosynthesis; Tumor-Cells,-Cultured; Tyrosine-metabolism
MESH: *Enzyme-Precursors-metabolism; *Integrins-metabolism; *Interleukin-1-biosynthesis; *Monocytes-metabolism; *Protein-Tyrosine-Kinase-metabolism; *Signal-Transduction
TG: Comparative-Study; Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.-; EC 2.7.1.-; EC 2.7.1.112; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 446-72-0; 55520-40-6; 70563-58-5
NM: endogenous-substrate-pp120; p72syk; Protein-Tyrosine-Kinase; Antigens,-CD29; Cell-Adhesion-Molecules; Enzyme-Precursors; Extracellular-Matrix-Proteins; Fibronectins; Integrins; Interleukin-1; Isoflavones; NF-kappa-B; Quinones; RNA,-Messenger; genistein; Tyrosine; herbimycin
AN: 95332324
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 30 of 125
TI: Up-regulation of integrin alpha 5 beta 1 expression by interleukin-6 in rabbit corneal epithelial cells.
AU: Ohashi-H; Maeda-T; Mishima-H; Otori-T; Nishida-T; Sekiguchi-K
AD: Research Institute, Osaka Medical Center for Maternal and Child Health, Japan.
SO: Exp-Cell-Res. 1995 Jun; 218(2): 418-23
ISSN: 0014-4827
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Interleukin-6 (IL-6) has been shown to promote the attachment of rabbit corneal epithelial cells to fibronectin-coated substratum and ex vivo migration of the cells on the corneal stroma. To examine whether IL-6 promotes cell attachment through up-regulation of expression of integrin alpha 5 beta 1, i.e., the major cell surface fibronectin receptor, we quantified the levels of both alpha 5 and beta 1 subunit transcripts by reverse transcription-polymerase chain reaction in cultured rabbit corneal epithelial cells pretreated with various concentrations of IL-6. The levels of both alpha 5 and beta 1 mRNAs were dose-dependently elevated by IL-6, attaining 1.5- and 1.8-fold increases, respectively, at 10 ng/ml. The stimulatory effect of IL-6 was transient; the levels of both subunit mRNAs reached a maximum 1 h after the addition of IL-6 and returned to the basal levels after 6 h. The IL-6-induced up-regulation of integrin alpha 5 and beta 1 mRNAs was also confirmed by Northern blot analysis. These results indicate that the increased attachment of corneal epithelial cells to fibronectin and enhanced ex vivo migration on corneal stroma by IL-6 is, at least in part, due to the temporal up-regulation of integrin alpha 5 beta 1 expression in corneal epithelial cells.
MESH: Amino-Acid-Sequence; Base-Sequence; Cells,-Cultured; Cornea-cytology; Corneal-Stroma-cytology; DNA-Primers; Integrins-chemistry; Molecular-Sequence-Data; Polymerase-Chain-Reaction; Rabbits-; Up-Regulation-Physiology
MESH: *Cornea-metabolism; *Integrins-biosynthesis; *Interleukin-6-pharmacology
TG: Animal; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0
NM: DNA-Primers; Integrins; Interleukin-6; Receptors,-Fibronectin
AN: 95317375
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 31 of 125
TI: Bryostatin 1 enhances lymphokine activated killer sensitivity and modulates the beta 1 integrin profile of cultured human tumor cells.
AU: Correale-P; Caraglia-M; Fabbrocini-A; Guarrasi-R; Pepe-S; Patella-V; Marone-G; Pinto-A; Bianco-AR; Tagliaferri-P
AD: Dipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Universita Federico II, Napoli, Italy.
SO: Anticancer-Drugs. 1995 Apr; 6(2): 285-90
ISSN: 0959-4973
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: Bryostatin 1 interferes with protein kinase C (PKC) signaling which is involved in the activation of human and murine cytotoxic T lymphocytes, and in the growth and differentiation of tumor cells. Bryostatin 1 has immunomodulating and antitumor properties as demonstrated by preclinical and clinical studies. Here we report that bryostatin 1 increases the susceptibility to lymphokine activated killers and modifies the pattern of beta 1 integrin expression of human tumor cells. On the basis of these results the use of bryostatin 1 in combination with immunostimulating cytokines such as interleukin-2 in the treatment of human cancer is suggested.
MESH: Tumor-Cells,-Cultured
MESH: *Adjuvants,-Immunologic-pharmacology; *Antineoplastic-Agents-pharmacology; *Integrins-analysis; *Killer-Cells,-Lymphokine-Activated-drug-effects; *Lactones-pharmacology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 83314-01-6
NM: Adjuvants,-Immunologic; Antigens,-CD29; Antineoplastic-Agents; Integrins; Lactones; bryostatin-1
AN: 95315599
UD: 9510
MEDLINE EXPRESS (R) 1991-1995 32 of 125
TI: Monocyte modulation of endothelial leukocyte adhesion molecules.
AU: Weill-D; Wautier-JL; Dosquet-C; Wautier-MP; Carreno-MP; Boval-B
AD: Laboratoire de Biologie Vasculaire et Cellulaire, Universite de Paris VII, France.
SO: J-Lab-Clin-Med. 1995 Jun; 125(6): 768-74
ISSN: 0022-2143
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Leukocyte adhesion to endothelium is dependent on expression of specialized molecules. Several of these molecules are upregulated by cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). We investigated the effect of medium conditioned by unstimulated (MCM) or stimulated monocytes and of recombinant cytokines on endothelial adhesion receptor expression. IL-1 beta, TNF-alpha, and MCM induced E-selectin similarly, whereas MCM induced VCAM-1 and ICAM-1 to a lesser extent than did TNF-alpha, and MCM induced VCAM-1 only weakly. The addition of pentoxifylline (10(-3) mol/L) to monocytes during MCM preparation blocked TNF-alpha production but not that of IL-1 beta or IL-6, and it reduced IL-1ra significantly (p < 0.05). When the MCM was devoid of TNF-alpha or when TNF-alpha was neutralized with a specific antibody, the action of MCM on E-selectin expression was significantly lower. Anti-IL-1 beta decreased the activity of MCM on endothelial E-selectin expression by about 50%. The effect of MCM on adhesion molecules was accompanied by an increase in monocyte adhesion. Inhibition of TNF-alpha production reduced monocytes adhesion slightly but significantly (18%, p < 0.05), whereas anti-IL-1 beta antibody decreased adhesion by 48% (p < 0.001). These results show that adherent monocytes released cytokines and antagonists that affect leukocyte adhesion receptors on endothelium differently from recombinant cytokines. E-selectin expression--and to a lesser extent ICAM expression--is modified, resulting in a modulation of leukocyte adhesion to endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
MESH: Cells,-Cultured; Culture-Media,-Conditioned; Endothelium,-Vascular-drug-effects; Gene-Expression-drug-effects; Integrins-analysis; Intercellular-Adhesion-Molecule-1-biosynthesis; Interleukin-1-biosynthesis; Interleukin-1-pharmacology; Interleukin-6-biosynthesis; Kinetics-; Pentoxifylline-pharmacology; Recombinant-Proteins-pharmacology; Sialoglycoproteins-biosynthesis; Sialoglycoproteins-pharmacology; Tumor-Necrosis-Factor-biosynthesis; Tumor-Necrosis-Factor-pharmacology; Umbilical-Veins
MESH: *Cell-Adhesion; *Cell-Adhesion-Molecules-biosynthesis; *Cytokines-pharmacology; *Endothelium,-Vascular-physiology; *Integrins-biosynthesis; *Leukocytes-physiology; *Monocytes-physiology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5; 6493-05-6
NM: interleukin-1-receptor-antagonist-protein; Cell-Adhesion-Molecules; Culture-Media,-Conditioned; Cytokines; E-Selectin; Integrins; Interleukin-1; Interleukin-6; Recombinant-Proteins; Sialoglycoproteins; Tumor-Necrosis-Factor; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1; Pentoxifylline
AN: 95287132
UD: 9509
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 33 of 125
TI: T lymphocyte locomotion in a three-dimensional collagen matrix. Expression and function of cell adhesion molecules.
AU: Friedl-P; Noble-PB; Zanker-KS
AD: Institute of Immunology, University of Witten/Herdecke, Germany.
SO: J-Immunol. 1995 May 15; 154(10): 4973-85
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: T cell locomotion within the extracellular matrix may be mediated by cell adhesion molecules. We investigated the expression and function of beta 1- and beta 2-integrins and CD44 on human peripheral CD4+ and CD8+ lymphocytes locomoting in a 3-D type I collagen matrix. Paths of randomly selected T cells were digitized from time-lapse videorecordings and were quantitatively analyzed. After the blocking of CD49b with mAb Gi9, the locomotion of a defined locomotor subset (50% of spontaneously locomoting cells) was inhibited. Anti-CD49d mAb HP2/1 and an activating anti-CD44 mAb (J173), respectively, induced transient recruitment (< 1 h) of previously nonmotile cells (10 to 35%). In contrast to the J173-induced short-term locomotion, hyaluronan incorporated within the matrix promoted locomotion for > 2 h. No significant effects were present for anti-CD49f (GoH3) and -CD11a (25.3) mAbs. After the addition of IL-8 to the matrix, rapid induction of locomotion in 20 to 30% of the cells (control) was evident, which was virtually abolished by anti-alpha 2- and alpha 6-integrin, and -CD11a mAbs. Thus, the locomotion of nonactivated and IL-8-activated T cells may involve different sets of integrins. Using flow cytometry, the development of a CD49b+CD29highCD44lowL-selectinlow T cell phenotype independent of activation markers including CD25, CD27, CD28, VLA-4, and CD45RA- to CD45RO-transition was observed after 4 days in the matrix. The initial development of spontaneous locomotion in the collagen matrix, however, was not accompanied by alterations in CAM surface staining and, therefore, may involve functional CAM activation rather than involving an increase in surface expression.
MESH: Antibodies,-Monoclonal-immunology; Antigens,-CD-biosynthesis; Cell-Adhesion-Molecules-biosynthesis; Cells,-Cultured; Collagen-; Culture-Media; Integrins-physiology; Interleukin-8-physiology; Lymphocyte-Function-Associated-Antigen-1-physiology; Receptors,-Very-Late-Antigen-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Cell-Movement-immunology; *T-Lymphocytes-physiology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 126880-86-2; 9007-34-5
NM: Antibodies,-Monoclonal; Antigens,-CD; Cell-Adhesion-Molecules; Culture-Media; Integrins; Interleukin-8; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Very-Late-Antigen; L-Selectin; Collagen
AN: 95248062
UD: 9508
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 34 of 125
TI: The adhesion molecules used by monocytes for migration across endothelium include CD11a/CD18, CD11b/CD18, and VLA-4 on monocytes and ICAM-1, VCAM-1, and other ligands on endothelium.
AU: Meerschaert-J; Furie-MB
AD: Program in Molecular and Cellular Biology, School of Medicine, State University of New York at Stony Brook 11794, USA.
SO: J-Immunol. 1995 Apr 15; 154(8): 4099-112
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: CD11/CD18 and VLA-4 integrins mediate interactions of monocytes with HUVEC cultured on human amniotic tissue. In the present study, the roles of individual CD11/CD18 integrins and endothelial adhesion molecules were examined using blocking mAbs and peptides. After 20 min of incubation, monocyte adhesion to and migration across unstimulated endothelium was dependent primarily on CD11a/CD18. When incubation was extended to 2 h to allow for completion of migration, either CD11a/CD18 or CD11b/CD18 could be used. Similarly, either CD11a/CD18 or CD11b/CD18 could be used by monocytes to bind to and traverse IL-1 beta-stimulated endothelium. Although both CD11a/CD18 and CD11b/CD18 are known to bind to ICAM-1, results of Ab-mixing experiments suggest that alternative ligands on HUVEC for CD11/CD18 integrins also may be used during transendothelial migration of monocytes. Our previous studies indicate that VLA-4 on monocytes interacts primarily with VCAM-1 on unstimulated endothelium. In contrast, migration of monocytes across IL-1 beta-stimulated endothelium was less dependent on VCAM-1. mAbs directed against binding sites for VLA-4 in domain 1 and domain 4 of VCAM-1 did not, by themselves, inhibit interactions of monocytes with stimulated HUVEC. VLA-4-dependent migration across IL-1 beta-stimulated endothelium was markedly inhibited only when mAbs to VCAM-1 were added in combination with peptides of fibronectin. Therefore, VLA-4 can interact with either VCAM-1 or alternative ligands on IL-1 beta-stimulated HUVEC-amnion cultures to mediate transendothelial migration of monocytes.
MESH: Amino-Acid-Sequence; Antigens,-CD11-physiology; Antigens,-CD18-physiology; Endothelium,-Vascular-drug-effects; Integrins-physiology; Intercellular-Adhesion-Molecule-1-physiology; Interleukin-1-pharmacology; Ligands-; Molecular-Sequence-Data; Peptides-chemistry; Receptors,-Very-Late-Antigen-physiology
MESH: *Cell-Adhesion-Molecules-physiology; *Cell-Movement; *Endothelium,-Vascular-cytology; *Monocytes-cytology
TG: Human; In-Vitro; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 126547-89-5
NM: Antigens,-CD11; Antigens,-CD18; Cell-Adhesion-Molecules; Integrins; Interleukin-1; Ligands; Peptides; Receptors,-Very-Late-Antigen; Vascular-Cell-Adhesion-Molecule-1; Intercellular-Adhesion-Molecule-1
AN: 95221918
UD: 9507
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 35 of 125
TI: Cell-mediated immune status of children with recurrent infection.
AU: Herrod-HG; Blaiss-MS; Valenski-WR; Gross-S
AD: Crippled Children's Foundation Research Center, Le Bonheur Children's Medical Center, University of Tennessee, Memphis 38163, USA.
SO: J-Pediatr. 1995 Apr; 126(4): 530-6
ISSN: 0022-3476
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: OBJECTIVE: To evaluate the cell-mediated immune status of children with recurrent respiratory tract infections. DESIGN: We evaluated the cell-mediated immune status of 76 patients referred because of recurrent infection. Patients were divided into those with serologic abnormalities and those without such findings. Twenty-three healthy children served as control subjects. Studies of lymphocyte phenotype included CD4+ CD29+ cells (an immunologically mature phenotype), lymphocyte proliferation studies, cytokine production including interleukin-2 (IL-2), IL-4, IL-6, and interferon gamma), and measurement of in vitro IgM and IgG synthesis. RESULTS: Lymphocyte proliferation and T-cell phenotype were similar in both patient groups as well as in control subjects. The proportions of CD4+ CD29+ cells at different ages were similar in all groups. Patients with serologic abnormalities (e.g., partial IgA deficiency, partial IgG subclass deficiency) produced more IL-2 and IL-4 than did other patients. The control population had greater spontaneous IgM and IgG synthesis than the patient groups. CONCLUSION: Routine studies of T-cell function of patients with recurrent infection provide little information useful in making clinical decisions.
MESH: Antigens,-Bacterial-biosynthesis; Bacterial-Vaccines-immunology; Child-; Child,-Preschool; IgG-blood; IgM-blood; Immunity,-Cellular-immunology; Immunophenotyping-; Infant-; Interferon-Type-II-blood; Interleukin-2-blood; Interleukin-4-blood; Interleukin-6-blood; Lymphocyte-Transformation; Matched-Pair-Analysis; Recurrence-
MESH: *Antigens,-CD-analysis; *Antigens,-CD4-analysis; *Cytokines-blood; *Immunity,-Cellular; *Integrins-analysis; *Respiratory-Tract-Infections-immunology
TG: Human
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 82115-62-6
NM: pneumovax; Antigens,-Bacterial; Antigens,-CD; Antigens,-CD29; Antigens,-CD4; Bacterial-Vaccines; Cytokines; IgG; IgM; Integrins; Interleukin-2; Interleukin-4; Interleukin-6; Interferon-Type-II
AN: 95213885
UD: 9507
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 36 of 125
TI: Interleukin-4 induces expression of the integrin alpha v beta 3 via transactivation of the beta 3 gene.
AU: Kitazawa-S; Ross-FP; McHugh-K; Teitelbaum-SL
AD: Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110.
SO: J-Biol-Chem. 1995 Feb 24; 270(8): 4115-20
ISSN: 0021-9258
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Osteoclastic bone resorption is dependent upon cell-matrix recognition. This process is mediated by the integrin alpha v beta 3 whose expression is enhanced, in avian osteoclast precursors, by bone-seeking steroids. The purpose of this study was to determine if bone-modulating cytokines impact on alpha v beta 3 expression by mouse marrow macrophages (BMMs), known to differentiate into osteoclasts. Of the cytokines tested. Interleukin-4 (IL-4) is most effective in increasing beta 3 mRNA levels by a mechanism involving transactivation of the beta 3 gene. Moreover, IL-4 augmented beta 3 mRNA is mirrored by plasma membrane appearance of alpha v beta 3. As IL-4 induces beta 3 and not alpha v mRNA, the beta 3 chain appears to regulate surface expression of the heterodimer. The functional significance of IL-4-induced alpha v beta 3 is underscored by the fact that, while attachment to fibronectin is unaltered, treatment of BMMs with the cytokine enhances alpha v beta 3-mediated binding to vitronectin 5-fold. Expression of this heterodimer by BMMs driven along a non-osteoclastic lineage suggests alpha v beta 3 may play a role in the inflammatory response of macrophages.
MESH: Cells,-Cultured; Cytokines-physiology; Glycoproteins-metabolism; Integrins-metabolism; Mice-; Protein-Binding; Receptors,-Cytoadhesin-metabolism; RNA,-Messenger-genetics; RNA,-Messenger-metabolism
MESH: *Gene-Expression-Regulation; *Integrins-genetics; *Interleukin-4-physiology; *Receptors,-Cytoadhesin-genetics; *Trans-Activation-Genetics
TG: Animal; Male; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
GS: bgr3
PT: JOURNAL-ARTICLE
CN: DE05413DENIDR; AR42404ARNIAMS
RN: 0; 0; 0; 0; 0; 0; 0; 0
NM: Cytokines; Glycoproteins; Integrins; Interleukin-4; Receptors,-Cytoadhesin; Receptors,-Vitronectin; RNA,-Messenger; Vitronectin
AN: 95181382
UD: 9506
MEDLINE EXPRESS (R) 1991-1995 37 of 125
TI: Cytokines modulate in vitro invasiveness of renal cell carcinoma cells through action on the process of cell attachment to endothelial cells.
AU: Yanase-M; Tsukamoto-T; Kumamoto-Y
AD: Department of Urology, School of Medicine, Sapporo Medical University, Japan.
SO: J-Urol. 1995 Mar; 153(3 Pt 1): 844-8
ISSN: 0022-5347
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Cytokines play important roles in adhesion between various cells and endothelium. Cell-cell adhesion is also a critical step in the invasion of interstitial tissue by cancer cells. Using an in vitro invasion assay modified by cultured human umbilical venule endothelial cells (HUVEC) and an extracellular matrix (Matrigel) membrane system, we studied how cytokines affect the invasiveness of human renal cell carcinoma cells through action on the endothelium. When HUVEC were treated for 6 hours with tumor necrosis factor (TNF, 100 or 1000 U/ml.), interleukin-1 (IL-1, 10 ng./ml.) or IL-6 (1.0 or 10 ng./ml.), the treatment significantly increased in vitro invasiveness of the carcinoma cells. Enhancement of carcinoma cell invasiveness reflected the enhancement by the cytokine treatments of the ability of HUVEC to express vascular cell adhesion molecule-1 (VCAM-1). Application of anti-VCAM-1 monoclonal antibody (mAb) suppressed in vitro invasion of the carcinoma cells when HUVEC were treated with the cytokines at the above concentrations. Moreover, an adherence assay demonstrated that a larger number of carcinoma cells adhered to the endothelium treated by the cytokines than to endothelium not receiving such treatment and that anti-VCAM-1 mAb application inhibited the adhesion. The cytokine treatment of HUVEC did not affect type IV collagenolysis. These results indicated that cytokines can enhance the in vitro invasiveness of carcinoma cells through their action on endothelium (that is, augmentation of VCAM-1 expression) in the in vitro invasion assay modified with HUVEC-Matrigel-reconstituted membrane.
MESH: Antibodies,-Monoclonal; Carcinoma,-Renal-Cell-metabolism; Cell-Adhesion; Cell-Adhesion-Molecules-biosynthesis; Cell-Adhesion-Molecules-immunology; Collagen-metabolism; Endothelium-cytology; Integrins-biosynthesis; Kidney-Neoplasms-metabolism; Neoplasm-Invasiveness; Tumor-Cells,-Cultured
MESH: *Carcinoma,-Renal-Cell-pathology; *Cytokines-physiology; *Kidney-Neoplasms-pathology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 9007-34-5
NM: Antibodies,-Monoclonal; Cell-Adhesion-Molecules; Cytokines; Integrins; Vascular-Cell-Adhesion-Molecule-1; Collagen
AN: 95165568
UD: 9505
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 38 of 125
TI: Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix.
AU: Boudreau-N; Sympson-CJ; Werb-Z; Bissell-MJ
AD: Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
SO: Science. 1995 Feb 10; 267(5199): 891-3
ISSN: 0036-8075
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Apoptosis (programmed cell death) plays a major role in development and tissue regeneration. Basement membrane extracellular matrix (ECM), but not fibronectin or collagen, was shown to suppress apoptosis of mammary epithelial cells in tissue culture and in vivo. Apoptosis was induced by antibodies to beta 1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1 beta converting enzyme (ICE) correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These results suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression.
MESH: Basement-Membrane; Cell-Line; Collagen-; Cysteine-Proteinase-Inhibitors-pharmacology; Cysteine-Proteinases-genetics; Extracellular-Matrix-metabolism; Fibronectins-; Gene-Expression-Regulation,-Enzymologic; Integrins-immunology; Mammae-enzymology; Metalloproteinases-genetics; Metalloproteinases-metabolism; Mice-; Mice,-Transgenic; RNA,-Messenger-genetics; RNA,-Messenger-metabolism; Transfection-
MESH: *Apoptosis-; *Cysteine-Proteinases-metabolism; *Extracellular-Matrix-physiology; *Mammae-cytology
TG: Animal; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-Non-P.H.S.; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA57621CANCI; ES07106ESNIEHS
RN: EC 3.4.22; EC 3.4.22.36; EC 3.4.24; EC 3.4.24.17; 0; 0; 0; 0; 0; 9007-34-5
NM: Cysteine-Proteinases; interleukin-1beta-converting-enzyme; Metalloproteinases; stromelysin-1; Antigens,-CD29; Cysteine-Proteinase-Inhibitors; Fibronectins; Integrins; RNA,-Messenger; Collagen
AN: 95149130
UD: 9505
MEDLINE EXPRESS (R) 1991-1995 39 of 125
TI: Comitogenic effects of very late activation antigens on CD3-stimulated human thymocytes. Involvement of various tyrosine kinase pathways.
AU: Ticchioni-M; Deckert-M; Bernard-G; Calandra-D; Breittmeyer-JP; Imbert-V; Peyron-JF; Bernard-A
AD: National Institute of Health and Medical Research (INSERM) Unit 343, Faculty of Medicine, Nice, France.
SO: J-Immunol. 1995 Feb 1; 154(3): 1207-15
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Thymocytes display several integrins that are involved in cell-extracellular matrix interactions and differentiation processes. We have examined the role of very late activation Ag (VLA) on human thymocyte stimulation. VLA-4, VLA-5, and VLA-6 activated with either mAbs or their natural ligands (fibronectin, laminin, and vascular cell adhesion molecule-1) are able to transduce costimulatory signals in thymocytes activated via the CD3 pathway, i.e., enhancement of thymocyte proliferation, CD25 and CD69 expression, and IL-2 secretion. In contrast, activation of thymocytes with a mitogenic pair of CD2 mAb was not modified by VLA molecules. Cross-linking of both beta 1- and alpha 5-chains induced tyrosine phosphorylation of several proteins, whereas the cross-linking of the alpha 4- and alpha 6-chains did not. Moreover, a different pattern of tyrosine phosphorylation was observed when thymocytes were activated via either beta 1- or alpha 5-chains. These results suggest that VLA molecules activate tyrosine kinase pathways in thymocytes, and that different pathways would be implicated during thymocyte interactions with extracellular matrix or accessory cells, which are likely to play a role in thymocyte differentiation.
MESH: Antibodies,-Monoclonal-immunology; Antigens,-CD-immunology; Antigens,-CD2-immunology; Cells,-Cultured; Child,-Preschool; Immunoblotting-; Integrins-immunology; Interleukin-2-immunology; Signal-Transduction-immunology; Thymus-Gland-cytology
MESH: *Antigens,-CD3-immunology; *Lymphocyte-Transformation-immunology; *Protein-Tyrosine-Kinase-immunology; *Receptors,-Very-Late-Antigen-immunology; *T-Lymphocytes-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.112; 0; 0; 0; 0; 0; 0; 0; 0
NM: Protein-Tyrosine-Kinase; Antibodies,-Monoclonal; Antigens,-CD; Antigens,-CD2; Antigens,-CD29; Antigens,-CD3; Integrins; Interleukin-2; Receptors,-Very-Late-Antigen
AN: 95123071
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 40 of 125
TI: Expression of vitronectin receptor on human NK cells and its role in protein phosphorylation, cytokine production, and cell proliferation.
AU: Rabinowich-H; Lin-WC; Amoscato-A; Herberman-RB; Whiteside-TL
AD: Department of Pathology, University of Pittsburgh School of Medicine, PA 15213.
SO: J-Immunol. 1995 Feb 1; 154(3): 1124-35
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: In this paper, we provide evidence that the vitronectin receptor (VNR) alpha v beta 3 is expressed on human NK cells. The presence of this VNR on freshly purified NK cells was demonstrated by flow cytometry analysis, as well as biochemically, after 125I-labeled surface lactoperoxidase labeling and immunoprecipitation. mAbs LM142 and LM609 specific for alpha v and alpha v beta 3, respectively, precipitated a heterodimer of alpha- and beta-chains with approximate molecular masses of 155 and 110 kDa under nonreducing conditions. Under reducing conditions, there was an apparent decrease in the molecular mass of the alpha-chain, which is likely to result from the release of a protein of 20 to 30 kDa linked by internal disulfide bond to the alpha v-chain. Integrin alpha v beta 3 expressed on NK cells became functional, i.e., was able to bind its ligand, vitronectin (VN), only after cellular activation or when costimulation with an additional signal was provided. Thus, NK cells adhered to plastic-immobilized VN only after IL-2 activation, and RGD-containing synthetic peptides or mAbs specific for alpha v beta 3 complex inhibited this binding. To assess the role of the VNR in signal transduction, anti-beta 3 mAb was used to cluster the VNR on NK cells and, thereby, mimic the process that occurs during formation of adhesive contacts. Cross-linking of VNR on fresh NK cells stimulated phosphorylation on tyrosine residues of several intracellular proteins. The major increase in tyrosine phosphorylation was observed in proteins of approximate molecular masses of 75 and 120 kDa. Therefore, signal transduction by the VNR on NK cells induced activation of intracellular protein kinases. Ligand engagement of the VNR on NK cells also costimulated cytokine production and proliferation of NK cells. Binding of NK cells to plastic-immobilized VN served as a costimulus with either anti-Fc gamma RIII or IL-2 to produce IFN-gamma, TNF-alpha, and cell proliferation. Our findings suggest that occupancy and subsequent clustering of VNRs play a role in the activation and function of human NK cells.
MESH: Amino-Acid-Sequence; Antibodies,-Monoclonal-immunology; Blotting,-Western; Cell-Adhesion-immunology; Flow-Cytometry; Integrins-biosynthesis; Interleukin-2-physiology; Molecular-Sequence-Data; Precipitin-Tests; Receptors,-Cytoadhesin-biosynthesis; Signal-Transduction-immunology; Up-Regulation-Physiology-immunology
MESH: *Cytokines-biosynthesis; *Integrins-immunology; *Killer-Cells,-Natural-immunology; *Lymphocyte-Transformation-immunology; *Protein-Tyrosine-Kinase-metabolism; *Receptors,-Cytoadhesin-immunology
TG: Human; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: EC 2.7.1.112; 0; 0; 0; 0; 0; 0
NM: Protein-Tyrosine-Kinase; Antibodies,-Monoclonal; Cytokines; Integrins; Interleukin-2; Receptors,-Cytoadhesin; Receptors,-Vitronectin
AN: 95123063
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 41 of 125
TI: IL-13 selectively induces vascular cell adhesion molecule-1 expression in human endothelial cells.
AU: Bochner-BS; Klunk-DA; Sterbinsky-SA; Coffman-RL; Schleimer-RP
AD: Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224.
SO: J-Immunol. 1995 Jan 15; 154(2): 799-803
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Previous studies with human umbilical vein endothelial cells (HUVEC) have shown that the cytokine IL-4 induces adherence of human eosinophils, but not neutrophils, because of its ability to selectively induce surface expression of vascular cell adhesion molecule-1 (VCAM-1). Because the cytokine IL-13 shares a number of biologic properties with IL-4, we examined the effect of IL-13 on the expression and function of adhesion molecules on HUVEC. Incubation of HUVEC for 4 to 48 h with IL-13 (0.1 to 15 U/ml) induced surface expression of VCAM-1, as detected by indirect immunofluorescence and flow cytometry, without significantly affecting expression of E-selectin or intercellular adhesion molecule-1. The kinetics and maximal IL-13-induced expression of VCAM-1 were similar to those seen with IL-4. Treatment of HUVEC with an optimal concentration of IL-13 (15 U/ml for 24 h) induced adhesiveness for eosinophils, but not for neutrophils, and adhesion was completely inhibited by mAb recognizing VCAM-1 or alpha 4 integrin (CD49d). These results demonstrate that IL-13, like IL-4, selectively stimulates HUVEC to express functional cell surface VCAM-1 and suggest a possible role for IL-13 in promoting VCAM-1/alpha 4 integrin-dependent accumulation of eosinophils during allergic and other inflammatory reactions in vivo.
MESH: Cell-Adhesion-Molecules-biosynthesis; Cells,-Cultured; Eosinophils-physiology; Integrins-biosynthesis; Integrins-physiology; Neutrophils-physiology; Umbilical-Veins-cytology
MESH: *Cell-Adhesion-physiology; *Cell-Adhesion-Molecules-physiology; *Endothelium,-Vascular-metabolism; *Interleukin-13-physiology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: AI27429AINIAID; HL49545HLNHLBI; AR31891ARNIAMS
RN: 0; 0; 0; 0; 143198-26-9
NM: Cell-Adhesion-Molecules; Integrins; Interleukin-13; Vascular-Cell-Adhesion-Molecule-1; alpha4-integrin
AN: 95114406
UD: 9504
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 42 of 125
TI: High expression of adhesion molecules/activation markers with little interleukin-2, interferon gamma, and tumor necrosis factor beta gene activation in fresh tumor-infiltrating lymphocytes from lung adenocarcinoma.
AU: Roussel-E; Gingras-MC; Grimm-EA; Roth-JA
AD: Department of Thoracic and Cardiovascular Surgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
SO: Cancer-Immunol-Immunother. 1995 Jul; 41(1): 1-9
ISSN: 0340-7004
PY: 1995
LA: ENGLISH
CP: GERMANY
AB: Little is known about the activation level of tumor-infiltrating lymphocytes (TIL) in human lung adenocarcinoma. We investigated the activation of fresh TIL at cellular and molecular levels and compared it with autologous and healthy normal peripheral blood lymphocytes (PBL) for baseline level. TIL were extracted from 12 primary lung adenocarcinomas by mechanical disruption without enzyme use and isolated by double-density Ficoll gradients. Flow-cytometry analysis of TIL subset distribution revealed that the majority was composed of T lymphocytes, and double labeling with alpha-CD3 and adhesion/activation markers revealed T cell subsets expressing CD49a, CD49b, CD54, and CD15, each of which was almost absent in autologous T peripheral blood lymphocytes (T-PBL). Moreover, the proportions of T-TIL expressing CD58, CD65, or CD25 were increased severalfold compared to T-PBL. Lymphokine gene activation in TIL was assessed by mRNA reverse transcriptase/polymerase chain reaction (RT-PCR) and primers for interleukin(IL)-2, IL-4, interferon (IFN) gamma, granulocyte/macrophage-colony-stimulating factor (GM-CSF), and tumor necrosis factor (TNF) beta. Semiquantitative comparisons between patients' TIL and PBL and healthy normal and activated PBL were performed by computerized image analysis. RT-PCR gel band products were quantified in relative units as a function of their size and intensity. TIL expressed detectable lymphokine mRNA but seemed poorly activated with respect to the total number of lymphokine genes and the amount of mRNA compared with alpha-CD3-activated healthy PBL. IL-2, IFN gamma, and TNF beta did not appear to be expressed at higher levels in TIL than in autologous or healthy normal PBL. However, two-thirds of the patients had TIL distinguishable from autologous PBL by specific expression of GM-CSF and from healthy normal PBL by expression of IL-4. These results show that lung adenocarcinoma TIL populations had little lymphokine gene activation despite the presence of several T cell subsets expressing different adhesion/activation markers. The lack or deficient combination of lymphokine production may be a factor that prevented efficient activation of TIL in these tumors.
MESH: Gene-Expression-Regulation,-Neoplastic; Immunophenotyping-; Integrins-metabolism; Lymphokines-genetics; Receptors,-Interleukin-2-metabolism; RNA,-Messenger-genetics
MESH: *Adenocarcinoma-immunology; *Cell-Adhesion-Molecules-metabolism; *Lung-Neoplasms-immunology; *Lymphocyte-Transformation; *Lymphocytes,-Tumor-Infiltrating-immunology
TG: Human; Support,-Non-U.S.-Gov't; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: CA45187CANCI; CA16672CANCI; 1P50CA5820403PP5CANCI
RN: 0; 0; 0; 0; 0
NM: Cell-Adhesion-Molecules; Integrins; Lymphokines; Receptors,-Interleukin-2; RNA,-Messenger
AN: 95368656
UD: 9511
MEDLINE EXPRESS (R) 1991-1995 43 of 125
TI: A hierarchy for integrin expression and adhesiveness among T cell subsets that is linked to TCR gene usage and emphasizes V delta 1+ gamma delta T cell adherence and tissue retention.
AU: Nakajima-S; Roswit-WT; Look-DC; Holtzman-MJ
AD: Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
SO: J-Immunol. 1995 Aug 1; 155(3): 1117-31
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: To define the relationship between T cell phenotype and adhesiveness, we examined T cell adhesion to endothelial cell, fibroblast, and epithelial cell monolayers as well as extracellular matrix proteins (collagen and fibronectin) using a three-color flow cytometry-based adherence assay that minimizes basal adhesion levels and facilitates quantitative lymphocyte subtyping. Regardless of monolayer type, monolayer stimulation conditions, or T cell activation status, we found that the gamma delta-TCR-bearing T cells adhered more efficiently than alpha beta T cells. The difference was based predominantly on increased levels of activatable LFA-1 (and to a lesser degree VLA-4) because: 1) it correlated precisely with inhibitability by anti-LFA-1 (and VLA-4) mAbs and the levels of LFA-1 (and VLA-4) on the cell surface, and 2) it persisted after maximal LFA-1 (and VLA-4) activation with phorbol dibutyrate. In contrast to most cases of alpha beta T cell behavior, gamma delta T cell adhesion to cell monolayers was not linked to memory status, i.e., there was no difference between naive V delta 1+ and memory V delta 2+ populations in levels of LFA-1 (or VLA-4) expression or LFA-1- (or VLA-4-) dependent adhesion to cell monolayers. However, V delta 1+ cells exhibited higher levels of VLA-5 that correlated with an increased adhesiveness to fibronectin and to a 120-kDa fibronectin fragment (FN-120) that contains only the VLA-5-binding domain but not to type I collagen or to a fibronectin fragment (FN-40) that binds only VLA-4. Taken together, the results define a hierarchy for integrin (LFA-1, VLA-4, and VLA-5) expression and consequent adhesion among T cell subsets that is linked to TCR gene usage (but not necessarily linked to memory status) and may thereby help to explain the accumulation and retention of V delta 1+ gamma delta T cells in epithelial and connective tissues.
MESH: Antibodies,-Monoclonal-immunology; Cell-Adhesion; Collagen-metabolism; Endothelium,-Vascular-physiology; Epithelium-physiology; Fibroblasts-physiology; Fibronectins-metabolism; Flow-Cytometry; Gene-Expression-Regulation-drug-effects; Immunologic-Memory; Integrins-physiology; Interleukin-1-pharmacology; Lymphocyte-Function-Associated-Antigen-1-genetics; Receptors,-Antigen,-T-Cell,-alpha-beta-genetics; Receptors,-Antigen,-T-Cell,-alpha-beta-physiology; Receptors,-Antigen,-T-Cell,-gamma-delta-physiology; Receptors,-Fibronectin-genetics; Receptors,-Very-Late-Antigen-genetics; Recombinant-Proteins-pharmacology; T-Lymphocyte-Subsets-drug-effects
MESH: *Gene-Rearrangement,-T-Lymphocyte; *Integrins-biosynthesis; *Lymphocyte-Function-Associated-Antigen-1-biosynthesis; *Receptors,-Antigen,-T-Cell,-gamma-delta-genetics; *Receptors,-Fibronectin-biosynthesis; *Receptors,-Very-Late-Antigen-biosynthesis; *T-Lymphocyte-Subsets-physiology
TG: Comparative-Study; Support,-U.S.-Gov't,-P.H.S.
PT: JOURNAL-ARTICLE
CN: HL40078HLNHLBI; HLAI51071HLNHLBI; HL07317HLNHLBI
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 0; 9007-34-5
NM: Antibodies,-Monoclonal; Fibronectins; Integrins; Interleukin-1; Lymphocyte-Function-Associated-Antigen-1; Receptors,-Antigen,-T-Cell,-alpha-beta; Receptors,-Antigen,-T-Cell,-gamma-delta; Receptors,-Fibronectin; Receptors,-Very-Late-Antigen; Recombinant-Proteins; Collagen
AN: 95363077
UD: 9511
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 44 of 125
TI: Extracellular matrix proteins and leukocyte function.
AU: Pakianathan-DR
AD: Department of Immunology, Genentech Inc., South San Francisco, CA 94080, USA.
SO: J-Leukoc-Biol. 1995 May; 57(5): 699-702
ISSN: 0741-5400
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: Extracellular matrix (ECM) proteins profoundly affect physiological functioning at the cellular level. Cell growth and differentiation, as well as cell shape and migration via the cytoskeleton, are all affected by ECM proteins. Leukocyte interactions with matrices have recently become an exciting field of research because a number of different leukocyte functions are significantly affected by their binding to ECM proteins. This may be especially important in inflammatory responses where leukocytes are primed for inflammatory mediator and cytokine production by binding to ECM proteins during extravasation. Because activated leukocytes produce potentially damaging substances, the progress of an inflammatory response can be profoundly affected by the ECM proteins encountered by leukocytes during their migration from within the peripheral circulation to sites of inflammation. This review summarizes recent publications describing components of the ECM that influence leukocyte function, the receptors involved in leukocyte binding to ECM proteins, and focuses on the effects of ECM proteins on the production of inflammatory mediators and cytokines by human peripheral blood leukocytes.
MESH: Cytokines-physiology; Inflammation-physiopathology; Integrins-physiology; Interleukin-8-biosynthesis; Phagocytosis-; Respiratory-Burst
MESH: *Cell-Adhesion-Molecules-physiology; *Extracellular-Matrix-physiology; *Extracellular-Matrix-Proteins-physiology; *Leukocytes,-Mononuclear-physiology; *Neutrophils-physiology; *Receptors,-Cytoadhesin-physiology
TG: Animal; Human
PT: JOURNAL-ARTICLE; REVIEW; REVIEW,-TUTORIAL
RN: 0; 0; 0; 0; 0; 0
NM: Cell-Adhesion-Molecules; Cytokines; Extracellular-Matrix-Proteins; Integrins; Interleukin-8; Receptors,-Cytoadhesin
AN: 95279871
UD: 9509
MEDLINE EXPRESS (R) 1991-1995 45 of 125
TI: In vivo blood monocyte migration to acute inflammatory reactions, IL-1 alpha, TNF-alpha, IFN-gamma, and C5a utilizes LFA-1, Mac-1, and VLA-4. The relative importance of each integrin.
AU: Issekutz-TB
AD: Department of Medicine, University of Toronto, Ontario, Canada.
SO: J-Immunol. 1995 Jun 15; 154(12): 6533-40
ISSN: 0022-1767
PY: 1995
LA: ENGLISH
CP: UNITED-STATES
AB: The role of the monocyte integrins, Mac-1, LFA-1, and VLA-4, on the adhesion of rat blood monocytes to rat microvascular endothelial cells in vitro and the importance of these receptors in monocyte migration to inflammation in vivo were evaluated. Monocyte adhesion to cytokine (IL-1, IFN-gamma, and TNF-alpha)-stimulated endothelial cells was mediated by Mac-1, LFA-1, and VLA-4, but Mac-1 appeared to be less important than LFA-1 or VLA-4. After i.v. injection, large numbers of 51Cr-labeled blood monocytes migrated within 2 h to dermal inflammatory sites induced by C5a, IL-1 alpha, IFN-gamma, TNF-alpha, LPS, and poly inosinic:cytidylic acid. Anti-Mac-1 mAb treatment had no effect, whereas anti-LFA-1 inhibited migration to C5a and the cytokines by 20 to 40%. Blocking both Mac-1 and LFA-1 decreased monocyte accumulation by 50 to 70% to all stimuli. Anti-VLA-4 inhibited monocyte migration to IL-1 alpha, IFN-gamma, TNF-alpha, and LPS, but not to C5a. Combining anti-Mac-1 with anti-VLA-4 did not increase this inhibition, whereas blocking VLA-4 and LFA-1 together further suppressed (60-85%) migration. Combined treatment with mAb to all three integrins inhibited > 98% of the monocyte migration to the inflammatory stimuli. In conclusion: 1) 51Cr blood monocytes can be used to quantify monocyte migration to inflammatory reactions in the rat. 2) Monocytes use Mac-1, LFA-1, and VLA-4 for in vitro adhesion and in vivo migration to cutaneous inflammation, and these integrins are essential for normal migration because blockade of all three virtually abolishes monocyte accumulation. 3) Mac-1 plays a less important role than LFA-1, as LFA-1 appears to substitute for Mac-1, and VLA-4 and LFA-1 can mediate much of the adhesion and migration. 4) The initiating inflammatory stimulus also modifies monocyte integrin usage, supporting the multistep combinatorial model of leukocyte extravasation.
MESH: Antibodies,-Monoclonal-pharmacology; Cell-Adhesion-physiology; Complement-5a-pharmacology; Dermatitis-etiology; Interferon-gamma,-Recombinant-pharmacology; Interleukin-1-pharmacology; Lymphocyte-Function-Associated-Antigen-1-physiology; Macrophage-1-Antigen-physiology; Rats-; Rats,-Inbred-Lew; Receptors,-Very-Late-Antigen-antagonists-and-inhibitors; Receptors,-Very-Late-Antigen-physiology; Recombinant-Proteins-pharmacology; Tumor-Necrosis-Factor-pharmacology
MESH: *Cell-Movement-physiology; *Integrins-physiology; *Monocytes-physiology
TG: Animal; Male; Support,-Non-U.S.-Gov't
PT: JOURNAL-ARTICLE
RN: 0; 0; 0; 0; 0; 0; 0; 0; 0; 80295-54-1
NM: Antibodies,-Monoclonal; Integrins; Interferon-gamma,-Recombinant; Interleukin-1; Lymphocyte-Function-Associated-Antigen-1; Macrophage-1-Antigen; Receptors,-Very-Late-Antigen; Recombinant-Proteins; Tumor-Necrosis-Factor; Complement-5a
AN: 95279808
UD: 9509
SB: AIM
MEDLINE EXPRESS (R) 1991-1995 46 of 125
TI: Interleukin-1 alpha stimulates keratinocyte migration through an epidermal growth factor/transforming growth factor-alpha-independent pathway.
AU: Chen-JD; Lapiere-JC; Sauder-DN; Peavey-C; Woodley-DT
AD: Department of Dermatology, Northwestern University School of Medicine, Chicago, IL 60611, USA.
SO: J-Invest-Dermatol. 1995 May; 104(5): 729-33
ISSN: 0022-202X
PY: