Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesion of electrically permeabilized platelets to collagen was found to be essentially independent of free Ca2+ concentration in the medium. Addition of stable GTP analogues increased the proportion of adhering cells about 5-fold. This effect was inhibited by guanosine 5'-[beta-thio]diphosphate, cytochalasin D or monoclonal antibodies to glycoprotein Ia. In contrast, the protein kinase C inhibitor staurosporine had only a small effect on the GTP-analogue-enhanced adhesion of the permeabilized cells to collagen. These results suggest that a guanine nucleotide regulatory (G)-protein is directly linked to the collagen receptor and is involved in the actin-dependent recruitment of additional collagen receptors.
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PMID:Evidence that adhesion of electrically permeabilized platelets to collagen is mediated by guanine nucleotide regulatory proteins. 141 28

Altered T cell adherence after human immunodeficiency virus 1 (HIV-1) infection may contribute to viral pathogenesis in the acquired immune deficiency syndrome. To address this hypothesis, we assessed mechanisms of T cell adherence to extracellular matrix proteins in vitro. We found that after HIV-1 infection, both chronically infected H9 CD4+ T cells and acutely infected primary peripheral blood lymphocytes acquired the ability to adhere to the extracellular matrix glycoprotein fibronectin, to a lesser extent to type IV collagen and laminin, but not to type I collagen. H9 cells chronically infected with two of the three HIV-1 strains studied showed approximately a sevenfold increase in attachment to fibronectin, while the same cells infected with the human retrovirus HIV-2 did not. Adhesion was accompanied by changes in morphology, including marked spreading and increased filopodia. These alterations were not blocked by the protein kinase C inhibitor H-7, which did inhibit TPA-induced T cell attachment to fibronectin. Monoclonal antibodies against both the alpha 5 and the beta 1 subunits of the classical fibronectin receptor as well as an Arg-Gly-Asp (RGD) peptide inhibited attachment, whereas anti-alpha 4 monoclonal antibodies and the CS1 peptide did not. Binding to collagen IV was also inhibited by the anti-beta 1 monoclonal antibody, but not the other antibodies. Cells metabolically labeled with [35S]methionine and analyzed by immunoprecipitation with polyclonal anti-beta 1 integrin antibody showed a 2.5-fold increase in integrin synthesis in infected cells compared to uninfected controls. This increase in synthesis was associated with an increase in cell surface expression of both alpha 5 and beta 1 integrins by FACS (registered trademark of Becton Dickinson for a fluorescence-activated cell sorter) analysis. Enhanced expression of integrins such as alpha 5 beta 1 may cause T cell adherence to a variety of tissues, where released viral gene products may induce some of the tissue-specific manifestations of HIV-1 infection.
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PMID:HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression. 183 Dec 4

Antigenic stimulation is associated with enhanced adhesion between T cells and antigen-presenting cells (APC). Binding of ligands to the T cell antigen receptor activates the adhesion function of lymphocyte function-associated molecule 1 (LFA-1; CD11a/CD18). We demonstrate here that ligand binding to major histocompatibility complex class II (Ia) molecules also activates LFA-1 function, providing a reciprocal mechanism for the induction of adhesion between T cells and Ia+ APC. Adhesion was affected by a qualitative change in LFA-1 molecules and was reversed by the protein kinase C inhibitor sphingosine. These results define a novel role for Ia molecules as signal transducing receptors that regulate LFA-1-dependent adhesion via a putative, Ia-coupled protein kinase(s).
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PMID:Engagement of major histocompatibility complex class II molecules induces sustained, lymphocyte function-associated molecule 1-dependent cell adhesion. 223 Jun 55

Polyunsaturated fatty acids influence several steps involved in metastasis formation in animal tumor models. During the process of metastasis from the primary site, tumor cells adhere to the endothelium and underlying basement membrane before extravasation and secondary growth. The purpose of this study was to determine the effect of unsaturated fatty acids on adhesion of human breast cancer cell lines to components of the basement membrane. Cells were cultured in low-serum medium for five days with or without added unsaturated fatty acids. Adhesion assays were conducted by incubating cells with basement membrane substrates coated on 96-well plates, washing to remove nonadherent cells, and staining adherent cells with crystal violet. Linoleic acid (LA) and eicosapentaenoic acid increased adhesion of the metastatic cell line MDA-MB-231 to Matrigel and type IV collagen, while eicosapentaenoic acid decreased adhesion of the less metastatic cell line SK-BR-3 to these two basement membrane substrates. Oleic acid increased adhesion of MDA-MB-231 cells to Matrigel and fibronectin. Nordihydroguaiaretic acid and high concentrations of indomethacin, each of which inhibits the lipoxygenase pathway of arachidonate metabolism, were effective in reversing the stimulatory effect of LA on MDA-MB-231 cell adhesion. A protein kinase C inhibitor likewise suppressed the increase in adhesion observed when MDA-MB-231 cells were incubated in media with added LA. Unsaturated fatty acids modified the adhesive properties of human breast cancer cell lines in vitro, and LA appeared to increase human breast cancer cell adhesion to extracellular matrix components by activating lipoxygenase and/or protein kinase C pathways.
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PMID:Unsaturated fatty acid effects on human breast cancer cell adhesion. 749 Dec 98

Tumor cell interaction with endothelial cells is a crucial step leading to organ-selective metastasis. Adhesion of murine B16 amelanotic melanoma cells (B16a) to murine microvascular endothelial cells (CD3) was enhanced, in a dose- and time-dependent manner, by pretreating CD3 cells with 12(S)-hydroperoxyeicosatetraenoic acid [i.e., 12(S)-HETE], a 12-lipoxygenase metabolite of arachidonic acid. The metabolic precursor of 12(S)-HETE, 12-HPETE (12-hydroperoxyeicosatetraenoic acid) also enhanced B16a cell adhesion to CD3 monolayers, whereas other lipoxygenase products, i.e., 5(S), 11(S), and 15(S)-HETEs were ineffective. 12(S)-HETE-enhanced tumor cell adhesion was blocked by treating endothelial cells with antibodies against the alpha v beta 3 complex or against individual subunits but not with antibodies against alpha 5 beta 1. In contrast, neither of these two integrins appeared to be involved in tumor cell adhesion to unstimulated endothelium. Flow cytometric analysis, immunofluorescent labeling, and image analysis indicated that 12(S)-HETE induced a time- and dose-dependent increase in the surface expression of alpha v beta 3 but not alpha 5 beta 1 on CD3 cells. The increased surface expression of alpha v beta 3 on endothelial cells did not result from an increased transcription or translation of alpha v beta 3 message as confirmed by quantitative reverse transcription-polymerase chain reaction, Northern blotting, and quantitative Western blotting. Instead, subcellular fractionation studies revealed an increased translocation of alpha v beta 3 integrins from the cytosolic pool to the membrane fractions. Pretreatment of endothelial cells with several cytoskeleton-disrupting agents (i.e., cycloheximide or acrylamide to disrupt intermediate filament vimentin, cytochalasin D to disrupt microfilaments, colchicine or Nocodazole to disrupt microtubules) abolished the 12(S)-HETE-enhanced alpha v beta 3 surface expression as well as tumor cell adhesion to endothelial cells. Also, pretreatment of CD3 cells with protein kinase C inhibitor calphostin C, but not with protein kinase A inhibitor H8, blocked 12(S)-HETE-enhanced alpha v beta 3 surface expression and tumor cell adhesion. Collectively, these results suggest that eicosanoid 12(S)-HETE modulates tumor cell interaction with endothelium via protein kinase C- and cytoskeleton-dependent up-regulation of the surface expression of alpha v beta 3 integrin.
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PMID:Activation of microvascular endothelium by eicosanoid 12(S)-hydroxyeicosatetraenoic acid leads to enhanced tumor cell adhesion via up-regulation of surface expression of alpha v beta 3 integrin: a posttranscriptional, protein kinase C- and cytoskeleton-dependent process. 831 70

Adhesion of RBL-2H3 mucosal mast cells to fibronectin-coated surfaces has been linked to changes in secretion and tyrosine kinase activity. We now show that adhesion affects the sensitivity of RBL cells to the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). In suspended cells, PMA inhibited antigen-induced calcium influx (as measured by manganese influx) and changes in intracellular free calcium and had complex effects on antigen-stimulated secretion. However, in adherent cells PMA had little effect on these responses. Suspended cells only secreted in response to thapsigargin if they were co-treated with PMA, while adherent cells secreted in response to thapsigargin alone. The thapsigargin-induced secretion in adherent cells was inhibited by protein kinase C down-regulation and by the protein kinase C inhibitor GF 109203X, but not by calphostin C. We suggest that protein kinase C is constitutively activated in adherent cells, possibly due to modification of the regulatory domain of the enzyme.
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PMID:Differential effects of the protein kinase C activator phorbol 12-myristate 13-acetate on calcium responses and secretion in adherent and suspended RBL-2H3 mucosal mast cells. 863 83

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

Phospholipase C secreted by bacterial pathogens has been identified as a virulence factor in several human diseases and has been implicated in impeding wound healing. The role of phospholipase C in the intracellular signal control of epithelial growth was studied in normal human skin keratinocytes cultured in conditions simulating aspects of wound healing. Bacillus cereus phospholipase C decreased cell-cell contact and increased cell migration resulting in disruption of the advancing epithelial sheet. Phospholipase C-induced migration was blocked by inhibitor of the phosphoinositol signal transduction pathway neomycin sulfate and protein kinase C inhibitor RO-31-8220. Induced migration was associated with elevated levels of matrix metalloproteinase-9 which, when blocked by tissue inhibitor of metalloproteinase-1, was accompanied by a loss of migration. Adhesion studies showed that phospholipase C treatment enhanced cell binding to fibronectin, vitronectin and collagen IV. Immunostained phospholipase C-stimulated cells cultured on fibronectin showed enhanced expression and relocation of the integrin subunits alpha(v), alpha5 and beta1. Confocal microscopy showed that phospholipase C-induced levels of integrin subunit beta1 were predominantly deposited on the basal surface of the cell apparently in focal contacts and associated with actin stress fibers. These results indicate that exogenous phospholipase C signaling from a bacterial source may play an important role in perturbing normal reepithelialization via altered expression of integrins and matrix metalloproteinase-9.
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PMID:Exogenous phospholipase C stimulates epithelial cell migration and integrin expression in vitro. 1135 Jun 46

The effect of alpha- and beta-tocopherol on human erythroleukemia cell (HEL) adhesion induced by phorbol 12-myristate 13-acetate (PMA) has been studied. Adhesion induced by PMA stimulation was prevented by 44.5% by physiological concentrations of alpha-tocopherol. Under the same experimental conditions, beta-tocopherol, an analogue of alpha-tocopherol, produced 11% inhibition of adhesion. Cell response gradually increased from 0 to 24 h of alpha-tocopherol treatment. Only a slight time dependency of beta-tocopherol inhibition was observed. Another human erythroleukemia cell line (K562) and the human monocyte tumor cell line U937 showed 5.0 and 11.2% inhibition, respectively. Similar to alpha-tocopherol, the protein kinase C inhibitor, Calphostin C, and the MAPK inhibitor, PD98059, prevented PMA-induced cell adhesion. An inhibition of ERK-1 phosphorylation was observed for alpha-tocopherol only in HEL, implying that MAP kinase pathway is involved in this cell line. Fluorescence-activated cell sorting (FACS), by using various integrin-specific monoclonal antibodies, has shown that alpha (1-6), beta1, and alphav integrins are less expressed at the cell surface after alpha-tocopherol treatment. Beta-tocopherol treatment was less effective.
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PMID:Differential inhibition by alpha- and beta-tocopherol of human erythroleukemia cell adhesion: role of integrins. 1139 Jan 83