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 of human neutrophils to endothelial cells is a crucial step during migration to the extravascular sites of inflammation. A large number of molecules, including the CD44 and LAM-1 antigens, have been described to participate in this process. We have investigated the regulation by human recombinant tumor necrosis factor-alpha (TNF-alpha) of human neutrophil plasma membrane expression of both CD44 and LAM-1 adhesion molecules, as well as that of CD43 sialophorin, which has been involved in adhesion and activation of leukocytes. The expression of these three antigens was down-regulated in neutrophils upon TNF-alpha treatment, as determined by immunofluorescence and immunoprecipitation experiments. However, the expression of other cell surface molecules, such as CD45 or CD11b, was up-regulated. Similar regulatory effects were also observed upon neutrophil treatment with other activating agents such as the chemoattractant peptide formyl-Met-Leu-Phe, the calcium ionophore A23187, or the phorbol ester phorbol 12-myristate 13-acetate. Protease inhibitors virtually abrogated the TNF-alpha-induced down-regulation of CD43 and CD44 expression, but not that of LAM-1, suggesting the involvement of a protease activity in this process. These results underline the role of TNF-alpha on the differential regulation of cell surface expression of neutrophil adhesion molecules, thus implying modifications in the neutrophil adhesive properties.
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PMID:Down-regulation by tumor necrosis factor-alpha of neutrophil cell surface expression of the sialophorin CD43 and the hyaluronate receptor CD44 through a proteolytic mechanism. 172 Oct 26

A high capacity semiautomated assay for neutrophil adhesion was developed utilizing the 96 well microtiter plate format. Optimal adhesion occurred with about 150 microliters/well of neutrophils at 5 X 10(6) cells/ml in tissue culture plates that had been precoated with 5% serum. Optimal incubation times were 10 min for f-Met-Leu-Phe-treated cells and 20 min for A23187 or phorbol myristate acetate stimulation. Optimal washing occurred after three washes with a Cetus Pro/pette pump. Adhesion could be effectively blocked by the inhibitors of cellular protein kinase C, an enzyme known to be necessary for the occurrence of neutrophil adhesion.
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PMID:Development of a high capacity microassay for measurement of neutrophil adhesion. 312 54

Expression of the leukocyte (beta 2) integrins is required for many functions of activated neutrophils (PMN), even when there is no recognized ligand for any beta 2 integrin. To investigate the hypothesis that beta 2 integrins may be involved in a signal transduction pathway related to cytoskeletal reorganization, we examined whether beta 2 integrins have a role in tyrosine phosphorylation of the cytoskeletal protein paxillin. Treatment of PMN in suspension with phorbol esters, f-Met-Leu-Phe, and TNF-alpha resulted in paxillin tyrosine phosphorylation. However, treatment of beta 2-deficient (LAD) PMN failed to induce paxillin tyrosine phosphorylation. Normal PMN phosphorylated paxillin in response to adhesion to immune complexes, while the LAD PMN did not. Adhesion of phorbol ester activated-LAD PMN to the extracellular matrix proteins fibronectin, laminin, and vitronectin failed to induce paxillin tyrosine phosphorylation. Treatment of activated normal PMN with mAb directed against the beta 2 integrin alpha chains demonstrated that CR3 (alpha M beta 2) was required for paxillin phosphorylation. Transfection of the cell line K562 with CR3 confirmed that CR3 ligation resulted in paxillin tyrosine phosphorylation. As a control, K562 transfected with CR2 (CD21) which bound equally avidly to the same complement C3-derived ligand (C3bi) as the CR3 transfectants, showed no enhanced tyrosine phosphorylation of paxillin upon receptor ligation. While both CR2 and CR3 transfectants showed efficient adhesion to a C3bi-coated surface, only the CR3 transfectants spread during adhesion and phosphorylated paxillin. Together these data demonstrate that CR3 is required for paxillin phosphorylation during activation of both adherent and nonadherent PMN. Even PMN activated in suspension or by adhesion to immune complexes, when no CR3 ligand is apparent, still require CR3 for a signal transduction pathway leading to paxillin tyrosine phosphorylation. This pathway is likely to be important for PMN function in inflammation and host defense.
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PMID:Complement receptor 3 (CR3, Mac-1, integrin alpha M beta 2, CD11b/CD18) is required for tyrosine phosphorylation of paxillin in adherent and nonadherent neutrophils. 752 4

The monomeric G-protein Ras is now considered to function as an initial regulator of multiple signaling pathways in both normal and transformed cell types. Adhesion and chemoattractant receptors are known to trigger activation of Ras in human neutrophils, but the signaling mechanism that activates Ras has only been partially elucidated. The present results show that in neutrophils, a time- and dose-dependent f-Met-Leu-Phe (FMLP)-induced activation of Ras is mediated by Gi2-proteins, because such activation is inhibited by pertussis toxin and because direct stimulation of heterotrimeric G-proteins with AlF4- is sufficient to activate Ras. Pretreatment of neutrophils with tyrosine kinase inhibitors, i.e. genistein or erbstatin that completely block FMLP-stimulated protein tyrosine phosphorylations, did not affect the FMLP-induced activation of Ras. Moreover, FMLP did not induce any detectable translocation of Grb2 and Sos to the plasma membrane of neutrophils. Other signaling molecules, such as protein kinase C, phosphatidylinositol 3-kinase and Ca2+, do not appear to be involved in the FMLP-induced Ras activation. Instead, stimulation of neutrophils with FMLP or C5a, the latter of which also activates Gi2-proteins, resulted in transient inhibition of the activity of Ras GTPase-activating proteins (GAP) with kinetics that correlated well with the kinetics of Ras activation. Moreover, decreased Ras-GAP activity was found in p120-GAP but not in neurofibromin immunoprecipitates of FMLP-stimulated cells. These results suggest that tyrosine kinase-dependent Ras exchange factors do not contribute to the FMLP-induced activation of Ras but that such activation is mediated via inhibition of p120-GAP in neutrophils.
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PMID:Chemotactic peptide-induced activation of Ras in human neutrophils is associated with inhibition of p120-GAP activity. 928 61

Deep vein thrombosis (DVT) is a low flow pathology often prevented by vascular compression to increase blood movement. We report new heterotypic adhesive interactions of normal erythrocytes operative at low wall shear rates (gamma(w)) below 100 s(-1). Adhesion at gamma(w) = 50 s(-1) of washed red blood cells (RBCs) to fibrinogen-adherent platelets was 4-fold less (P <.005) than to collagen-adherent platelets (279 +/- 105 RBC/mm(2)). This glycoprotein VI (GPVI)-triggered adhesion was antagonized (> 80% reduction) by soluble fibrinogen (3 mg/mL) and ethylenediaminetetraacetic acid (EDTA). RBC-platelet adhesion was reduced in half by antibodies against CD36 or GPIb, but not by antibodies against GPIIb/IIIa, von Willebrand factor (VWF), thrombospondin (TSP), P-selectin, beta(1), alpha(v), or CD47. Adhesion of washed RBCs to fibrinogen-adherent neutrophils was increased 6-fold in the presence of 20 microM N-formyl-Met-Leu-Phe to a level of 67 RBCs per 100 neutrophils after 5 minutes at 50 s(-1). RBC-neutrophil adhesion was diminished by anti-CD11b (76%), anti-RBC Landsteiner-Wiener (LW) (ICAM4; 40%), or by EDTA (> 80%), but not by soluble fibrinogen or antibodies against CD11a, CD11c, CD36, TSP, beta(1), alpha(v), or CD47. RBC adhesion to activated platelets and activated neutrophils was prevented by wall shear stress above 1 dyne/cm(2) (at 100 s(-1)). Whereas washed RBCs did not adhere to fibrin formed from purified fibrinogen, adhesion was marked when pure fibrin was precoated with TSP or when RBCs were perfused over fibrin formed from recalcified plasma. Endothelial activation and unusually low flow may be a setting prone to receptor-mediated RBC adhesion to adherent neutrophils (or platelets/fibrin), all of which may contribute to DVT.
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PMID:Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma. 1239 14

1. Adhesion of neutrophils (PMNs) to vascular endothelial cells (EC) is a critical step in recruitment and infiltration of leukocytes into tissues during inflammation. Substance P (SP), a neuropeptide released from sensory nerves, evoked PMN adhesion to EC. The NK receptor subtype(s) and the cell type(s) involved were investigated. 2. SP was coincubated with human PMNs and EC from the human umbilical vein (HUVEC); adhesion was quantitated by computerised microimaging fluorescence analysis. 3. The proadhesive effects of SP (range 10(-18)-10(-6) M) were illustrated in a biphasic dose-response curve, with a maximum at 10(-15) M (276+/-16% adhesion vs control; P<0.01) and another one at 10(-10) M (200+/-18% adhesion vs control; P<0.01). Neurokinin A was less active and neurokinin B was inactive. The adhesion molecules LFA-1 and OKM-1, but not selectins, were involved according to results with selective mAbs. 4. The NK(1) agonist [Sar(9),Met(O(2))(11)]SP reproduced the effects of SP, whereas the NK(2) agonist [betaAla(8)]-neurokininA (4-10) acted at 10(-13)-10(-8) M only. The NK(3) agonist, senktide, was ineffective. 5. The NK(1) antagonists, CP 96,345 and L 703,606 (both 10(-6) M), abolished the effect of 10(-15) M SP and inhibited that of 10(-10) M SP by 56+/-5% (P<0.01). By comparison, the NK(2) antagonist, SR 48,968 (10(-7) M), partially antagonised the adhesion evoked by 10(-10) M SP (% inhibition: 61+/-6; P<0.05). 6. Since preincubation of PMNs and HUVEC with SP gave the same results it is clear that both cell types contributed to its proadhesive effects. 7. These results indicate that SP induced a proadhesive effect during inflammatory processes, which was mediated by NK(1) and NK(2) receptors.
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PMID:Substance P increases neutrophil adhesion to human umbilical vein endothelial cells. 1287 28

Glycosphingolipids (GSLs) at the cell surface membrane are associated or complexed with signal transducers (Src family kinases and small G-proteins), tetraspanins, growth factor receptors, and integrins. Such organizational framework, defining GSL-modulated or -dependent cell adhesion, motility, and growth, is termed "glycosynapse" (Hakomori, S., and Handa, K. (2002) FEBS Lett. 531, 88-92; Hakomori, S. (2004) Ann. Braz. Acad. Sci. 76, 553-572). We describe here the functional organization of the glycosynaptic microdomain, and the mechanisms for control of cell motility and invasiveness, in normal bladder epithelial HCV29 cells versus highly invasive bladder cancer YTS1 cells, both derived from transitional epithelia. (i) Ganglioside GM2, but not GM3 or globoside, interacted specifically with tetraspanin CD82, and such a complex inhibited hepatocyte growth factor (HGF)-induced activation of Met tyrosine kinase in a dose-dependent manner. (ii) Depletion of GM2 in HCV29 cells by treatment with D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4), or reduction of CD82 expression by RNA interference, significantly enhanced HGF-induced Met tyrosine kinase and cell motility. (iii) In contrast, YTS1 cells, lacking CD82, displayed HGF-independent activation of Met tyrosine kinase and high cell motility. Transfection of the CD82 gene to YTS1 inhibited HGF dose-dependent Met tyrosine kinase activity and cell motility, due to formation of the GM2-CD82 complex. (iv) Adhesion of YTS1 or YTS1/CD82 cells to laminin-5-coated plates, as compared with noncoated plates, strongly enhanced Met activation, and the degree of activation was further increased in association with GSL depletion by P4. Laminin-5-dependent Met activation was minimal in HCV29 cells. These findings indicate that GSL, particularly GM2, forms a complex with CD82, and that such complex interacts with Met and thereby inhibits HGF-induced Met tyrosine kinase activity, as well as integrin to Met cross-talk.
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PMID:Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse. 1721 49

We describe a quantitative assay of the strength of adhesion of activated and nonactivated human neutrophils to a substratum, which is carried out in a custom-made microfluidic device. The strength of adhesion is quantified by the fraction of cells remaining adherent (ACF) after a given time of exposure to shear stress in a test microchannel. The microfluidic device is made of two layers of poly(dimethylsiloxane) with integrated membrane valves. This construction allows concurrent testing of two different populations of cells, as well as setting well-defined times of exposure of cells to stress and of their incubation prior to the exposure. The test microchannels have a tapered profile, exposing cells to nearly an order of magnitude range of shear stress. ACF is measured periodically by computer-controlled videomicroscopy scans of the device, with up to 60,000 individual cells identified within a 90 seconds scan. The high throughput of the scans allows reliable quantitative assessment of the ACF. Adhesion of untreated neutrophils and neutrophils activated with formyl-Met-Leu-Phe was tested concurrently in a series of experiments with a fibrinogen-coated glass substratum. At optimized testing conditions, the ACF of activated cells was consistently found to be three times higher than that of nonactivated cells. An adhesion assay could be completed within 11 min from the loading of cells into the device without any intervention by the operator. The proposed device and assay could be used to assess the state of activation of neutrophils in human blood with a potential application to diagnostics of inflammation.
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PMID:Quantitative measurements of the strength of adhesion of human neutrophils to a substratum in a microfluidic device. 1730 8

Adhesions remain a significant complication of abdominal surgery. There is a growing body of evidence suggesting that remodeling of peritoneal extracellular matrix by matrix metalloproteinases (MMPs) is involved in adhesion formation. We have shown that administration of a specific neurokinin-1 receptor (NK-1R) antagonist (CJ-12,255, Pfizer) to rats within 5 hours of surgery reduces intraabdominal adhesion formation. Because substance P (SP), the primary NK-1R ligand, is known to augment tissue fibrosis, the aim of this study was to determine the effects of NK-1R antagonist administration on peritoneal MMP expression and activity 24 hours after surgery in a rat adhesion model. Following laparotomy, four ischemic buttons were created on the peritoneum of rats that received either an intraperitoneal NK-1R antagonist or a vehicle at surgery. Adhesion formation was assessed 7 days later. Peritoneal fluid and tissue were collected at 24 hours to assess total MMP activity, as well as MMP-2, MMP-8, and MMP-9 activity. Specific MMP and tissue inhibitors of MMP mRNAs were measured, and the effects of SP on MMP-3 expression were determined in Met-5A cells, a human peritoneal mesothelial cell line. NK-1R antagonist administration reduced adhesion formation by 47% (p<0.05) at 7 days and significantly increased the total MMP activity in peritoneal fluid at 24 hours. There was an accompanying increase (p<0.05) in MMP-8 and MMP-9 mRNA expression and activity in peritoneal tissue and fluid, respectively. MMP-3 mRNA was also increased in the 24-hour peritoneal tissue, and exposure of Met-5A cells to SP reduced MMP-3 expression and activity. These data support a role for MMPs, specifically MMP-3, MMP-8, and MMP-9, in intraabdominal adhesion formation and suggest that the NK-1R antagonist may reduce adhesions, in part, by increasing MMP activity in the peritoneum by 24 hours after surgery.
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PMID:A neurokinin-1 receptor antagonist that reduces intraabdominal adhesion formation increases peritoneal matrix metalloproteinase activity. 1802 27

Many bacterial pathogens that invade non-phagocytic cells first interact with host cell surface receptors. Adhesion to the host cell is followed by the activation of specific host signalling pathways that mediate bacterial internalization. The food-borne Gram-positive bacterium Listeria monocytogenes makes use of two surface proteins, internalin (InlA) and InlB to engage in a species-specific manner the adhesion molecule E-cadherin and the hepatocyte growth factor receptor Met, respectively, to induce its internalization. After entry, Listeria has the capacity to spread from cell to cell and disseminate to its target organs after breaching the intestinal, blood-brain and placental barriers in human. InlA but not InlB is critical for the crossing of the intestinal barrier, whereas the conjugated action of both InlA and InlB mediates the crossing of the placental barrier. Here we review the InlA-E-cadherin interaction, the signalling downstream of this interaction, the molecular mechanisms involved in bacterial internalization and the role of InlA-E-cadherin interaction in the breaching of host barriers and the progression to listeriosis. Together, this review illustrates how in vitro data were validated by epidemiological approaches and in vivo studies using both natural hosts and genetically engineered animal models, thereby elucidating key issues of listeriosis pathophysiology.
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PMID:Listeria monocytogenes internalin and E-cadherin: from structure to pathogenesis. 1919 87

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