UMLS:C0001511 - FACTA Search

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

Adhesion between platelets and polymorphonuclear leukocytes (PMN) is a key event in thrombosis and inflammation. Double color fluorescence-activated cell sorter (FACS) analysis was used to determine the extent and kinetics of adhesion of thrombin-activated platelets to resting or activated PMN when mixed cell populations were incubated in dynamic conditions. Activated platelets bound very rapidly to PMN. Mixed cell conjugates reached a maximum at 1 minute and were reversible within 10 minutes. Platelet/PMN adhesion required both Ca2+ and Mg2+ and was markedly increased by the presence of Mn2+. The latter made mixed cell conjugates stable up to 10 minutes. Adhesion of platelets required metabolic activity of PMN and was abolished by tyrosine kinase inhibitors. Furthermore, adhesion of platelets to PMN resulted in binding of a monoclonal antibody (MoAb 24) known as beta 2 integrins "activation reporter." When PMN were activated by exogenous stimuli, the adhesion of platelets was markedly increased: fMLP induced a rapid and transient effect, while PMA resulted in a slower, but stable, increase in mixed conjugates formation. The hypothesis that activated PMN beta 2 integrins are able to bind a counter-receptor on platelets was directly demonstrated by the increase of mixed cell conjugates following PMN treatment with KIM127 and KIM185, two anti-CD18 antibodies able to induce the active conformation of beta 2 integrins. Consistently, two other anti-CD18, as well as an anti-CD11b inhibitory antibody abolished platelet/PMN adhesion. PMN beta 2 integrin activation was not the only mechanism for activated platelet/PMN adhesion to occur: indeed, this phenomenon could also be inhibited by two anti-P-selectin antibodies. Resting platelets did not adhere to resting PMN, but markedly adhered to fMLP- or PMA-activated PMN. Resting platelet/fMLP-activated PMN adhesion was abolished by anti-CD18 antibodies, but not by anti-P-selectin antibodies. In conclusion, activated platelet/PMN interaction can be modeled as an adhesion cascade involving a P-selectin-dependent recognition step and a functional signal. The latter proceeds through tyrosine kinase activation and enables a beta 2 integrin-dependent adhesion to a not yet identified counter-receptor constitutively expressed on platelet surface.
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PMID:Platelet/polymorphonuclear leukocyte interaction in dynamic conditions: evidence of adhesion cascade and cross talk between P-selectin and the beta 2 integrin CD11b/CD18. 894 53

We have shown recently that mouse small cerebellar neurons adhere to a short amino acid sequence of the G2 domain of the laminin alpha 1 chain via the cell surface-expressed HNK-1 carbohydrate. Therefore, we were interested in identifying glycoproteins carrying the HNK-1 carbohydrate at the cell surface of these neurons. Adhesion of small cerebellar neurons to laminin is partially dependent on Ca2+, Mn2+, and Mg2+, indicating the involvement of integrins, which were identified as beta 1, alpha 3, and alpha 6. They could be shown to bind to laminin by a beta 1-dependent adhesion mechanism. None of these subunits was found to carry the HNK-1 carbohydrate. HNK-1-immunoreactive glycoproteins were immunoprecipitated and shown to consist of predominantly one molecular species, which was identified as the neural cell recognition molecule L1. L1 was demonstrated to bind in a concentration-dependent and saturating manner to laminin. The binding could be partially inhibited by Fab fragments of monoclonal antibodies against the HNK-1 carbohydrate and against the Ig-like domains of L1. Furthermore, antibodies to the Ig-like domains of L1 and beta 1 integrin inhibited partially cell adhesion to laminin. Determination of the association of L1, beta 1 integrin, and the HNK-1 carbohydrate on the cell surface of live cerebellar neurons by antibody-induced patching and copatching revealed HNK-1 to be linked to L1, but less so to beta 1 integrin. However, only negligible association was found between L1 and beta 1 integrin. Furthermore, it could be shown that adhesion to laminin is mediated by L1/HNK-1- and beta 1 integrin-dependent mechanisms that act at least partially independent of each other.
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PMID:L1/HNK-1 carbohydrate- and beta 1 integrin-dependent neural cell adhesion to laminin-1. 900 39

Chondroadherin (the 36-kD protein) is a leucine-rich, cartilage matrix protein known to mediate adhesion of isolated chondrocytes. In the present study we investigated cell surface proteins involved in the interaction of cells with chondroadherin in cell adhesion and by affinity purification. Adhesion of bovine articular chondrocytes to chondroadherin-coated dishes was dependent on Mg2+ or Mn2+ but not Ca2+. Adhesion was partially inhibited by an antibody recognizing beta1 integrin subunit. Chondroadherin-binding proteins from chondrocyte lysates were affinity purified on chondroadherin-Sepharose. The beta1 integrin antibody immunoprecipitated two proteins with molecular mass approximately 110 and 140 kD (nonreduced) from the EDTA-eluted material. These results indicate that a beta1 integrin on chondrocytes interacts with chondroadherin. To identify the alpha integrin subunit(s) involved in interaction of cells with the protein, we affinity purified chondroadherin-binding membrane proteins from human fibroblasts. Immunoprecipitation of the EDTA-eluted material from the affinity column identified alpha2beta1 as a chondroadherin-binding integrin. These results are in agreement with cell adhesion experiments where antibodies against the integrin subunit alpha2 partially inhibited adhesion of human fibroblast and human chondrocytes to chondroadherin. Since alpha2beta1 also is a receptor for collagen type II, we tested the ability of different antibodies against the alpha2 subunit to inhibit adhesion of T47D cells to collagen type II and chondroadherin. The results suggested that adhesion to collagen type II and chondroadherin involves similar or nearby sites on the alpha2beta1 integrin. Although alpha2beta1 is a receptor for both collagen type II and chondroadherin, only adhesion of cells to collagen type II was found to mediate spreading.
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PMID:Integrin alpha2beta1 is a receptor for the cartilage matrix protein chondroadherin. 928 92

We have examined the functional status of the VLA-4/alpha4beta1 integrin in a panel of human melanoma cell lines, focusing on the ability of cells expressing alpha4beta1 to mediate adhesion to the alpha4-specific ligands CS-1 peptide and VCAM-1. All melanoma cells expressing alpha4pbeta1 (8 of 10 lines examined) were capable of adhering to these specific ligands in adhesion assays, whereas 2 cell lines (HMB2 and VUP) which lacked surface alpha4 were unable to do so. Adherence of different melanoma cell lines to VCAM-1 was relatively uniform and not susceptible to upregulation with known integrin-activating factors, such as manganese ions, phorbol ester and activating monoclonal antibody (mAb) TS2/16. Cell adhesion to CS-1 peptide, however, varied according to cell surface receptor density and, in some cases, could be up-regulated by integrin-activating factors. Adhesion of SK23 cells to CS-1 peptide was increased by all 3 activating stimuli, whereas for all other melanoma cells an increase was obtained only by the use of TS2/16 mAb. Our data indicate not only an unusually low activation state of alpha4beta1 in SK23 cells but also heterogeneity in the activating capacity of the various stimuli. Moreover, a protein kinase C-dependent role in alpha4beta1 activity was suggested by adhesion assays carried out in the presence of the protein kinase C inhibitor calphostin C, which considerably reduced adhesion to CS-1 peptide.
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PMID:Activation status and function of the VLA-4 (alpha4beta1) integrin expressed on human melanoma cell lines. 933 53

Adhesion to extracellular matrices is known to modulate leukocyte activation, although the mechanisms are not fully understood. Mononuclear phagocytes are exposed to fibrinous provisional matrix throughout migration into inflammatory foci, so this study was undertaken to determine whether fibrinogen triggers activation of NF-kappa B transcription factors. U937 cells differentiated with PMA in nonadherent culture were shown to express two fibrinogen-binding integrins, predominately CD11b/CD18, and to a lesser extent, CD11c/CD18. Cells stimulated with fibrinogen (10-100 microg/ml)/Mn2+ (50 microM) for 2 h were examined by electrophoretic mobility shift assay. NF-kappa B activation, minimal in unstimulated cells, was substantially up-regulated by fibrinogen. Fibrinogen also caused activation of AP-1, but not SP1 or cAMP response element-binding protein (CREB) factors. Blocking mAbs against CD18 and CD11b abrogated fibrinogen-induced NF-kappa B activation. To determine the effects on transcriptional regulation, U937 cells were transfected with a plasmid containing the HIV-1 enhancer (bearing two NF-kappa B sites) coupled to a chloramphenicol acetyltransferase (CAT) reporter. Cells were subsequently stimulated with 1) PMA for 24 h, inducing CAT activity by 2.6-fold, 2) fibrinogen/Mn2+ for 2 h, inducing CAT activity by 3.2-fold, or 3) costimulation with fibrinogen and PMA, inducing 5.7-fold the CAT activity induced by PMA alone. We conclude that contact with fibrinogen-derived proteins may contribute to mononuclear phagocyte activation by signaling through CD11b/CD18, resulting in selective activation of transcriptional regulatory factors, including NF-kappa B.
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PMID:Fibrinogen activates NF-kappa B transcription factors in mononuclear phagocytes. 968 12

Adhesion to collagens by most cell types is mediated by the integrins alpha1beta1 and alpha2beta1. Both integrin alpha subunits belong to a group which is characterized by the presence of an I domain in the N-terminal half of the molecule, and this domain has been implicated in the ligand recognition. Since purified alpha1beta1 and alpha2beta1 differ in their binding to collagens I and IV and recognize different sites within the major cell binding domain of collagen IV, we investigated the potential role of the alpha1 and alpha2 I domains in specific collagen adhesion. We find that introducing the alpha2 I domain into alpha1 results in surface expression of a functional collagen receptor. The adhesion mediated by this chimeric receptor (alpha1-2-1beta1) is similar to the adhesion profile conferred by alpha2beta1, not alpha1beta1. The presence of alpha2 or alpha1-2-1 results in preferential binding to collagen I, whereas alpha1 expressing cells bind better to collagen IV. In addition, alpha1 containing cells bind to low amounts of a tryptic fragment of collagen IV, whereas alpha2 or alpha1-2-1 bearing cells adhere only to high concentrations of this substrate. We also find that collagen adhesion of NIH-3T3 mediated by alpha2beta1 or alpha1-2-1beta1, but not by alpha1, requires the presence of Mn2+ ions. This ion requirement was not found in CHO cells, implicating the I domain in cell type-specific activation of integrins.
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PMID:Role of the I-domain in collagen binding specificity and activation of the integrins alpha1beta1 and alpha2beta1. 969 16

The multipotential cytokine transforming growth factor-beta (TGF-beta) is secreted in a latent form. Latency results from the noncovalent association of TGF-beta with its processed propeptide dimer, called the latency-associated peptide (LAP); the complex of the two proteins is termed the small latent complex. Disulfide bonding between LAP and latent TGF-beta-binding protein (LTBP) produces the most common form of latent TGF-beta, the large latent complex. The extracellular matrix (ECM) modulates the activity of TGF-beta. LTBP and the LAP propeptides of TGF-beta (isoforms 1 and 3), like many ECM proteins, contain the common integrin-binding sequence RGD. To increase our understanding of latent TGF-beta function in the ECM, we determined whether latent TGF-beta1 interacts with integrins. A549 cells adhered and spread on plastic coated with LAP, small latent complex, and large latent complex but not on LTBP-coated plastic. Adhesion was blocked by an RGD peptide, and cells were unable to attach to a mutant form of recombinant LAP lacking the RGD sequence. Adhesion was also blocked by mAbs to integrin subunits alphav and beta1. We purified LAP-binding integrins from extracts of A549 cells using LAP bound to Sepharose. alphavbeta1 eluted with EDTA. After purification in the presence of Mn2+, a small amount of alphavbeta5 was also detected. A549 cells migrated equally on fibronectin- and LAP-coated surfaces; migration on LAP was alphavbeta1 dependent. These results establish alphavbeta1 as a LAP-beta1 receptor. Interactions between latent TGF-beta and alphavbeta1 may localize latent TGF-beta to the surface of specific cells and may allow the TGF-beta1 gene product to initiate signals by both TGF-beta receptor and integrin pathways.
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PMID:Interactions between growth factors and integrins: latent forms of transforming growth factor-beta are ligands for the integrin alphavbeta1. 972 16

We recently reported that the heparin (Hep) III domain of fibronectin contains the H2 cell adhesion site in repeat III5 which binds activated alpha4 integrins. We have now further characterized the heparin and cell binding activities of this domain. A recombinant fragment containing repeats III4-III5 (FN-III4-5) induced Jurkat cell adhesion upon integrin activation with Mn2+ or TS2/16 monoclonal antibody (anti-beta1). Adhesion of Mn2+-treated cells to FN-III4-5 or FN-III5 fragments was inhibited by chondroitinase ABC and ACII but not by the anti-alpha4 monoclonal antibody HP2/1. In contrast, HP2/1 completely blocked adhesion of TS2/16-treated cells while chondroitinase had a partial (FN-III4-5) or minor (FN-III5) effect. Thus, the role of each receptor depended on the stimulus used to activate alpha4 beta1. The combination of HP2/1 and chondroitinase at dilutions which did not inhibit when used individually abolished adhesion of Mn2+ or TS2/16-treated cells to both fragments, indicating a cooperative effect between alpha4beta1 and chondroitin sulfate proteoglycans (CSPG). Furthermore, we have identified a 20-amino acid sequence in III5 (HBP/III5) which binds heparin and induces cell adhesion via CSPG exclusively. Although soluble HBP/III5 was a poor inhibitor, when combined with H2, it abolished adhesion to FN-III4-5 and FN-III5 fragments. These results establish that adhesion to the Hep III domain involves the cooperation of activated alpha4 beta1 and CSPG and show that HBP/III5 is a novel heparin and CSPG-binding site contributing to cell adhesion to this domain.
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PMID:Cooperative role for activated alpha4 beta1 integrin and chondroitin sulfate proteoglycans in cell adhesion to the heparin III domain of fibronectin. Identification of a novel heparin and cell binding sequence in repeat III5. 986 21

Metargidin (ADAM-15) is a type I transmembrane glycoprotein belonging to the ADAM (A Disintegrin and Metalloprotease Domain) family of proteins and is widely expressed in different tissues and cell types. Members of this family contain an amino-terminal metalloprotease domain followed by a disintegrin domain, a cysteine-rich region and a membrane proximal EGF-like domain. The disintegrin domain of metargidin contains an RGD tripeptide sequence, suggesting that it may potentially interact with the integrin family of proteins. Here we identify integrin ligands for metargidin on haemopoietic cells, by using a chimeric protein containing the extracellular domain of metargidin fused to the Fc portion of human IgG. Binding activity to a panel of human cell lines was analysed by solid-phase cell-adhesion assays. Metargidin bound to a monocytic cell line, U937, and a T cell line, MOLT-4, in a specific manner. Adhesion was divalent cation- and temperature- dependent and strongly enhanced by Mn2+, all features of integrin-mediated binding. Using a panel of anti-integrin antibodies we show that alphavbeta3 is a ligand for metargidin on U937 cells. In contrast, for MOLT-4 cells, the integrin alpha5beta1 contributes to cell binding. Adhesion was mediated by the disintegrin domain of metargidin as RGD-based peptides inhibited cell binding to both cell lines. The specificity of the interaction between both alphavbeta3 and alpha5beta1 and metargidin was further confirmed by solid-phase adhesion assays using purified recombinant integrins. These results together indicate that metargidin can function as a cell adhesion molecule via interactions with alphavbeta3 and alpha5beta1 integrins.
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PMID:Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells. 991 69

A simple and convenient assay for the simultaneous measurement of eosinophil and neutrophil adhesion is described. Incubations were performed in microtitre plates coated with different proteins. Adhesion of eosinophils and neutrophils was determined by the use of specific radioimmunoassays for eosinophil cationic protein (ECP) and myeloperoxidase (MPO). Using this assay, Mn2+ induced a significant increase of the adhesion of eosinophils to plasma fibronectin and fibrinogen in a time-dependent fashion, while a small increase of the adhesion of neutrophils to these two proteins was observed. In contrast, a time-dependent potent increment of the adhesion of both eosinophils and neutrophils to tissue fibronectin and albumin was found. Tissue fibronectin preferentially supported eosinophil adhesion compared with that of neutrophils in the presence of Mn2+. PMA (10(-9) mol/l) induced a significant increase in the adhesion of eosinophils and neutrophils of the same pattern to all four proteins. However, when granulocytes were stimulated by Mn2+ in combination with PMA, eosinophils and neutrophils showed different patterns of response to plasma fibronectin and fibrinogen, respectively, but the same pattern of response to tissue fibronectin. f-MLP stimulated an early increase of the adhesion of neutrophils to fibrinogen, while a weak stimulation of the adhesion of eosinophils to plasma fibronectin and fibrinogen and of neutrophils to plasma fibronectin was observed. Co-stimulation with f-MLP and Mn2+ did not induce any additive effects on granulocyte adhesion. In conclusion, the assay allows rapid quantification of eosinophil and neutrophil adhesion and can be used to directly compare the response of neutrophils and eosinophils. The assay is thus suitable for studies aimed at identifying agents with a selective effect on either of the cells.
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PMID:Simultaneous analysis of eosinophil and neutrophil adhesion to plasma and tissue fibronectin, fibrinogen, and albumin. 1041 Sep 75

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