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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion molecules are likely to play a role in the process of tumour progression. We investigated the expression of integrins, ICAM-1, and CD44 and the influence of interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), and tumour necrosis factor-alpha (TNF-alpha) on expression of these molecules on four uveal melanoma cell lines. The in vitro integrin expression was quite variable. The alpha V and beta 1 subunits were expressed on all cell lines, and none of the cell lines showed any alpha 3, beta 2, or beta 4 expression. Other integrin subunits showed a more variable pattern. ICAM-1 and CD44 were strongly expressed on all cell lines. IFN-alpha, IFN-gamma, and TNF-alpha upregulated alpha 1, alpha 2, and alpha 3 expression, and did not alter alpha 4, alpha 5, alpha 6, beta 2, alpha v beta 3, and beta 4 expression. The effects on alpha V and alpha V beta 5 were variable. ICAM-1 was upregulated by IFN-gamma and TNF-alpha, but not by IFN-alpha. Cytokine treatment hardly changed CD44 expression. In one case a comparison was made between expression on cultured cells and on tissue sections of the tumour of origin. Differences in expression were observed for the integrin subunits alpha 2, alpha 3, and alpha 5. This study shows that integrins and ICAM-1 expression on uveal melanoma cells in vitro are susceptible to cytokine treatment, but that the effects on integrin expression are cytokine and cell line dependent. Furthermore, some differences in integrin expression between cells in vivo and in vitro exist.
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PMID:Cytokine-mediated modulation of integrin, ICAM-1 and CD44 expression on human uveal melanoma cells in vitro. 749 58

Integrin expression and function is largely modulated by cell activation. Here we provide evidence that long term activation of human NK cells results in a marked modulation of beta 1-integrin expression and adhesive functions. By flow cytometry and immunochemical analysis we have detected induction of alpha 1 beta 1 and alpha 2 beta 1, increased expression of alpha 4 beta 1 and alpha 5 beta 1, and decline of alpha 6 beta 1 on CD3-CD56+ NK cells generated from 10-day coculture of nonadherent PBMC with irradiated RPMI 8866 EBV+ lymphoblastoid B cell line. Adhesion assays performed on extracellular matrix-coated plates showed that, unlike fresh NK cells, long term-activated NK cells bind to native collagen I via alpha 2 beta 1 and to heat-denatured collagen I in an RGD-dependent manner, although they lose the ability to bind to laminin. In regard to the adhesion to FN, no major quantitative changes are observed after long term NK cell activation. However, whereas alpha 4 beta 1 and alpha 5 beta 1 completely mediate the adhesion of fresh NK cells to fibronectin, binding of activated NK cells is only partially beta 1-dependent and seems to involve also non-beta 1-integrin(s) recognizing and RGD sequence. The modulation of beta 1-integrin expression and the acquisition of new adhesive properties on long term-activated NK cells may be relevant for their traffic and tissue localization during inflammation and immune response.
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PMID:Long term activation of natural killer cells results in modulation of beta 1-integrin expression and function. 750 24

We studied the expression of integrin alpha and beta chains on alveolar epithelia in normal and fibrotic lung tissue by immunohistochemistry. Alveolar epithelia and their precursor cells in fetal lung tissue consistently expressed alpha 1, alpha 2, alpha v and beta 1 chains. Neoexpression of alpha 4, alpha 6 and beta 4 chains was detected on alveolar epithelia of fibrotic lung tissue. Adhesion blocking assays with isolated type II pneumocytes were performed to investigate the substrate specificity of the alpha chains. alpha 1, alpha 2 and alpha 3 demonstrated a specificity for collagen, alpha 4, alpha 5 and alpha 6 for fibronectin, alpha 3 and alpha 6 for laminin and finally alpha 5 and alpha v for vitronectin.
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PMID:[Pattern of expression of integrins in alveolar epithelia of fetal and adult lungs and interstitial lung diseases]. 751

The modulation of adhesive interaction between lymphocyte progenitors and bone marrow stroma may critically determine the maturation and migration of B cell progenitors. mAb against CD9 and beta 1 integrins are reported to induce the homotypic adhesion of pre-B cells. We present evidence that the anti-CD9 mAb 50H.19 and ALB6 but not the proaggregatory anti-VLA-4 mAb 44H6 also enhance the Fc-independent heterotypic adhesion of the human pre-B cell lines NALM-6 and HOON to bone-marrow stromal fibroblasts (BM-FB) but not to bone marrow stroma. CD9-enhanced binding of NALM-6 cells to BM-FB was inhibited 58% by the anti-VLA-4 mAb HP2/1, 36% by the anti-VLA-5 mAb BIIG2, and 99% by their combination. The mAb effectively inhibited adhesion when prebound to NALM-6 cells but not when prebound to BM-FB. The anti-VCAM-1 mAb E1/6 inhibited CD9-enhanced adhesion by only 14% suggesting the involvement of other ligands. Adhesion was inhibited by mAbs against the COOH-terminus and central cell binding domains of fibronectin, as well as by the corresponding CS1 and RGD peptides. Adhesion was not affected by H-7 and sphingosine, inhibitors of protein kinase C. These results suggest that perturbation of CD9 on pre-B cells promotes recognition of stromal cell fibronectin by VLA-4 and VLA-5 and implicates CD9 as a novel regulator of inside-out signaling relevant to B lymphopoiesis.
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PMID:CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin. 751 26

We have investigated which integrins mediate the elevation of intracellular calcium ([Ca2+]i) triggered by spreading of endothelial cells on fibronectin (FN). Specific anti-integrin monoclonal antibodies immobilized on glass surfaces were used as agonists to trigger cell spreading. These experiments demonstrated that an antibody to alpha v could induce the rise in [Ca2+]i, whereas two antibodies to alpha 5 beta 1 were inactive, despite their ability to induce cell spreading and elevation of intracellular pH. Antibodies in solution were then used as agonists to block association of specific integrins with FN. These experiments also showed that alpha v integrin(s) but not alpha 5 beta 1 mediated the rise in [Ca2+]i in cells spreading on FN. Adhesion assays in the presence of function-blocking anti-integrin antibodies and affinity chromatography on FN columns of surface-labeled cell extracts were carried out to characterize the integrins that bind to FN. Both methods showed that alpha v integrin(s) and alpha 5 beta 1 participate in FN binding; however, the contribution from alpha v integrin(s) was much less than that of alpha 5 beta 1. These results demonstrate that two receptors for FN on the same cells can trigger distinct intracellular signaling pathways and, furthermore, that an integrin whose contribution to adhesion is barely detectable can have a major effect on cellular responses. The results also suggest that the specificity for activation of the calcium signaling pathway resides primarily in the integrin alpha subunit.
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PMID:Alpha v integrins mediate the rise in intracellular calcium in endothelial cells on fibronectin even though they play a minor role in adhesion. 751 59

Fibronectin (FN)-mediated cell adhesion is controlled mainly by alpha 5 beta 1 (recognizing the RGD sequence) and alpha 4 beta 1 (recognizing the CS-1 peptide sequence of FN) integrin receptors. Integrin-dependent cell adhesion to FN is greatly promoted by optimal GM3 concentration at the surface membrane (Zheng, M., Fang, H., Tsuruoka, T., Tsuji, T., Sasaki, T., and Hakomori, S. (1993) J. Biol. Chem. 268, 2217-2222), and cell adhesion mediated by alpha 4 beta 1 (to FN) or alpha 6 beta 1 (to laminin) is inhibited by modifying N-glycosylation processing of the integrin receptor (e.g. Akiyama, S. K., Yamada, S. S., and Yamada, K. M. (1989) J. Biol. Chem. 264, 18011-18018). We therefore studied the specific role of N-glycosylation in alpha 5 beta 1 function. Key findings of the present study were as follows. (i) Adhesion of K562 cells to FN-coated plates, which is mediated solely by alpha 5 beta 1, was inhibited when cells were treated with a mixture of endo-N-acetylglucosaminidase F and peptide -N4-(N-acetylglucosaminyl)asparagine amidase F (endo-F/PNGase-F). (ii) The alpha 5 beta 1 receptor at the K562 cell surface tended to dissociate into alpha 5 and beta 1 subunits when an extract of cells treated with endo-F/PNGase-F was precipitated by integrin subunit-specific antibodies, i.e. the alpha 5 subunit was preferentially precipitated by anti-alpha 5 monoclonal antibody ZH5, and the beta 1 subunit was preferentially precipitated by anti-beta 1 monoclonal antibody ZH1. When intact cells were extracted and treated with either ZH5 or ZH1, both alpha 5 and beta 1 were coprecipitated, indicating that the two subunits are normally tightly associated with each other. (iii) Adhesion of alpha 5 beta 1-containing liposomes (phosphatidylcholine:cholesterol liposomes incorporating purified alpha 5 beta 1) to FN-coated plates was abolished by treatment of liposomes with endo-F/PNGase-F. Liposomes incorporating alpha 5 beta 1 pretreated with endo-F/PNGase-F also did not bind to FN. When purified alpha 5 beta 1 receptor was treated with endo-F/PNGase-F followed by ZH5 or ZH1, the alpha 5 or beta 1 subunit was precipitated separately, respectively. In contrast, both subunits were always coprecipitated when intact purified alpha 5 beta 1 receptor was directly treated with ZH5 or ZH1. These findings indicate that N-glycosylation of both the alpha and beta subunits of the alpha 5 beta 1 integrin receptor is essential for association of these subunits and for optimal binding to FN.
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PMID:Functional role of N-glycosylation in alpha 5 beta 1 integrin receptor. De-N-glycosylation induces dissociation or altered association of alpha 5 and beta 1 subunits and concomitant loss of fibronectin binding activity. 751 65

Adhesion of human platelets to type I collagen under arterial flow conditions is extremely fast, being mediated primarily by the alpha 2 beta 1 integrin (glycoprotein Ia/IIa). We have investigated the involvement of cyclic nucleotides in platelet adhesion to soluble native collagen immobilized on Sepharose beads using a new microadhesion assay under arterial flow conditions. To prevent platelet stimulation by thromboxanes and adenosine diphosphate (ADP), experiments were performed with aspirin-treated platelets in the presence of ADP-removing enzyme systems such as creatine phosphate/creatine phosphokinase or apyrase. Rapid reciprocal changes in platelet adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) occurred during adhesion. cAMP levels in adherent platelets were 2.4-fold lower than in effluent platelets or in static controls, whereas cGMP levels were increased 2.4-fold. These results suggest that contact between platelets and collagen stimulates guanylate cyclase and inhibits adenylate cyclase. This occurs in the absence of the platelet release reaction. We also studied short-term effects of agents that regulate cyclic nucleotide synthesis, prostaglandin E1 (PGE1) and sodium nitroprusside (SNP). After only 3.8 seconds at 10 to 30 dyne/cm2, PGE1 (10 mumol/L) increased cAMP 16.4-fold, whereas SNP (50 mumol/L) increased cGMP ninefold and caused a 3.2-fold increase in cAMP. Both PGE1 and SNP rapidly (< 5 seconds) inhibited platelet adhesion in a dose-dependent manner that was correlated with the increase in cyclic nucleotides. Our data suggest that cAMP and cGMP play a regulatory role in the initial phases of platelet adhesion to collagen mediated by the alpha 2 beta 1 integrin receptor.
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PMID:Role of cyclic nucleotides in rapid platelet adhesion to collagen. 751 2

Platelet adhesion has been measured to type-I monomeric collagen, collagen fibres, alpha 1(I) and alpha 2(I) chains and the chain fragments alpha 1(I)CB3, alpha 1(I)CB6, alpha 1(I)CB7 and alpha 1(I)CB8, and alpha 2(I)CB3,5 and alpha 2(I)CB4. Little if any adhesion occurred to any denatured species at 37 degrees C, demonstrating the importance of the collagen helix. However, on coating at 4 degrees C to promote helix formation, and assaying at room temperature to avoid denaturation, adhesion was observed to both alpha-chain types and all fragments, the exact level of which depended on the identity of the species in question. Adhesion was strongly Mg(2+)-dependent. Antibodies against the integrin alpha 2 beta 1 partially inhibited adhesion to alpha-chains and all fragments except alpha 1(I)CB6, indicating a wide distribution of alpha 2 beta 1-binding sites in the collagen molecule. 'Activation-dependent' adhesion to monomeric collagen, totally secondary to alpha 2 beta 1-mediated adhesion, involved at least two mechanisms, one mediated by integrin alpha IIb beta 3 and insensitive to prostaglandin E1, the other inhibitable by prostaglandin E1 but independent of integrin alpha IIb beta 3. alpha IIb beta 3-mediated adhesion to fragments was, at least in part, independent of the alpha 2 beta 1-mediated adhesion. Adhesion to fibres was largely bivalent-cation-independent with only minor involvement of integrin alpha 2 beta 1. Some alpha IIb beta 3-mediated adhesion occurred but was independent of any alpha 2 beta 1-initiated adhesion. Total 'activation-dependent' adhesion to fibres was less than to monomeric collagen. Affinity chromatography revealed bivalent-cation-independent binding to fibres of three main platelet surface proteins, 90, 150 and 190 kDa in size.
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PMID:Conformation-dependent platelet adhesion to collagen involving integrin alpha 2 beta 1-mediated and other mechanisms: multiple alpha 2 beta 1-recognition sites in collagen type I. 751 71

Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.
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PMID:Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. 751 18

The integrin supergene family includes receptors for a variety of extracellular matrix as well as cell surface proteins. Integrin alpha 4 has been shown to play an important role in leukocyte adhesion and extravasation during immune and inflammatory reactions. One recognition sequence known to interact with alpha 4 is the Leu-Asp-Val (LDV) site contained in the connecting segment 1 region of fibronectin. Here we present evidence that shows that a conformationally restricted RGD-containing peptide is a potent inhibitor of cell adhesion mediated by alpha 4 beta 1, a receptor not convincingly documented to interact with RGD peptides. This peptide, 1-adamantaneacetyl-Cys-Gly-Arg-Gly-Asp-Ser-Pro-Cys (disulfide bridge between residues 1-8), blocks Jurkat cell adhesion to connecting segment 1-containing peptides as well as cell adhesion to cytokine-activated endothelial cells. Adhesion of Jurkat cells to either vascular cell adhesion molecule-expressing cells or recombinant vascular cell adhesion molecule-coated plates was likewise inhibited by this peptide. Furthermore, alpha 4 beta 1 can bind directly to a cyclic RGD peptide immobilized to Sepharose. Integrins, alpha 5 beta 1, alpha v beta 3, alpha IIb/beta IIIa, alpha 2 beta 1, alpha v beta 1, alpha v beta 5, alpha v beta 6, and alpha 3 beta 1, have been shown to recognize the Arg-Gly-Asp (RGD) sequence present in a variety of extracellular matrix proteins, and our data support the addition of alpha 4 beta 1 to this group. Further studies using molecular modeling of such cyclic RGD peptides could help in the design of more potent peptides or nonpeptide mimetics that could effectively block alpha 4-mediated activity and have potential application in a number of inflammatory diseases.
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PMID:Cyclic RGD peptide inhibits alpha 4 beta 1 interaction with connecting segment 1 and vascular cell adhesion molecule. 751 41


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