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 Staphylococcus aureus to human endothelial cells is implicated in the pathogenesis of invasive staphylococcal disease. The adhesion to endothelial cells of isogenic mutants defective in defined surface structures was studied. Three strains of S. aureus defective in fibronectin-binding proteins FnBPA and FnBPB showed reduced adhesion. This was fully restored by complementation of a FnBPA- FnBPB- mutant derived from strain 8325-4 with a multicopy plasmid encoding FnBPA or FnBPB. Adhesion of mutants defective in other surface structures was unaffected. Anti-fibronectin antibodies blocked adhesion of 8325-4 to endothelial cells, while adhesion of strains 8325-4, P1 and five clinical isolates was inhibited by the recombinant form of the binding domain of FnBPB (rFNBD) from Streptococcus dysgalactiae. Adherence of bacterial aggregates resulting from the presence of purified fibrinogen was also inhibited by rFNBD protein. Three strains of S. aureus defective in FnBPA and FnBPB were not internalized by endothelial cells. S. aureus FnBPs mediate adhesion to human endothelial cells and are required for subsequent internalization, interactions of potential relevance to pathogenesis and treatment.
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PMID:Bacterial fibronectin-binding proteins and endothelial cell surface fibronectin mediate adherence of Staphylococcus aureus to resting human endothelial cells. 1062 45

The effect of specific chemical functionalities on the adhesion of polymorphonuclear leukocytes (PMNs) under flow was investigated using a set of well-characterized, chemically functionalized surfaces prepared by self-assembly of alkanethiolate monolayers on gold surfaces. Terminal functionalities included CH(3), CH(2)OH, COOH, and (OCH(2)CH(2))(3)OH groups. A new surface modification was used to incorporate a phosphorylcholine moiety on the hydroxyl-terminated monolayer. Surface modification was verified using contact-angle measurements, ellipsometry, and X-ray photoelectron spectroscopy. Adhesion on the surfaces was studied in the presence and absence of pre-adsorbed fibrinogen. Fibrinogen adsorption on self-assembled monolayers (SAMs) was quantified using radioisotope detection. PMN adhesion was found to be dependent on the monolayer's terminal functionality. Adhesion was higher on the hydrophobic CH(3) surface and the polar COOH monolayer. Leukocyte adhesion was least on the phosphorylcholine-rich surface, followed by the ethylene-oxide-containing monolayer. Cell adhesion also was low on the hydrophilic OH monolayer. Attachment was decreased with increasing shear rate, exhibiting a three-fold decrease between 20 and 100 s(-1). Fibrinogen adsorption was higher on the CH(3) monolayer but comparable for the other four SAMs. Preincubation of the surfaces with fibrinogen decreased adhesion on all SAMs examined.
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PMID:Leukocyte adhesion on model surfaces under flow: effects of surface chemistry, protein adsorption, and shear rate. 1073 70

Adhesion and signaling by integrins require their dynamic association with nonintegrin membrane proteins. One such protein, the glycolipid-anchored urokinase receptor (uPAR), associates with and modifies the function of the beta(2)-integrin Mac-1 (CD11b/CD18). In this study, a critical non-I-domain binding site for uPAR on CD11b (M25; residues 424-440) is identified by homology with a phage display peptide known to bind uPAR. Recombinant soluble uPAR and cells expressing uPAR bound to immobilized M25, binding being promoted by urokinase and blocked by soluble M25, but not a scrambled control or homologous peptides from other beta(2)-associated alpha-chains. Mac-1, but not a mutated Mac-1 in which M25 was replaced with the homologous sequence of CD11c, co-precipitated with uPAR. In the beta-propeller model of alpha-chain folding, M25 spans an exposed loop on the ligand-binding, upper surface of alphaM, identifying uPAR as an atypical alphaM ligand. Although not blocking ligand binding to Mac-1, M25 (25-100 microM) inhibited leukocyte adhesion to fibrinogen, vitronectin, and cytokine-stimulated endothelial cells. M25 also blocked the association of uPAR with beta(1)-integrins and impaired beta(1)-integrin-dependent spreading and migration of human vascular smooth muscle cells on fibronectin and collagen. These observations indicate that uPAR associates with integrins directly and that disruption of this association broadly impairs integrin function, suggesting a novel strategy for regulation of integrins in the settings of inflammation and tumor progression.
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PMID:Identification of a urokinase receptor-integrin interaction site. Promiscuous regulator of integrin function. 1074 8

This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody causes platelet aggregation and granule secretion. A physiological role for the F11R protein was demonstrated by its phosphorylation after the stimulation of platelets by thrombin and collagen. A pathophysiological role for the F11R was revealed by demonstrating the presence of F11R-antibodies in patients with thrombocytopenia. Adhesion of platelets through the F11R resulted in events characteristic of the action of cell adhesion molecules (CAMs). To determine the structure of this protein, we cloned the F11R cDNA from human platelets. The predicted amino acid sequence demonstrated that it is an integral membrane protein and an immunoglobulin superfamily member containing 2 extracellular C2-type domains. The structure of the F11R as a member of a CAM family of proteins and its activity in mediating adhesion confirm each another. We conclude that the F11R is a platelet-membrane protein involved in 2 distinct processes initiated on the platelet surface. The first is antibody-induced platelet aggregation and secretion that are dependent on both the FcgammaRII and the GPIIb/IIIa integrin and that may be involved in pathophysiological processes associated with certain thrombocytopenias. The second is an F11R-mediated platelet adhesion that is not dependent on either the FcgammaRII or the fibrinogen receptor and that appears to play a role in physiological processes associated with platelet adhesion and aggregation. (Blood. 2000;95:2600-2609)
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PMID:Cloning of the human platelet F11 receptor: a cell adhesion molecule member of the immunoglobulin superfamily involved in platelet aggregation. 1075 40

Integrin receptor alpha(2)beta(1) requires micromolar Ca(2+) to bind to collagen and to the peptide GPC(GPP)(5)GFOGER(GPP)(5)GPC (denoted GFOGER-GPP, where O represents hydroxyproline), which contains the minimum recognition sequence for the collagen-binding alpha(2) I-domain (Knight, C. G., Morton, L. F., Peachey, A. R., Tuckwell, D. S., Farndale, R. W., and Barnes, M. J. (2000) J. Biol. Chem. 275, 35-40). Platelet adhesion to these ligands is completely dependent on alpha(2)beta(1) in the presence of 2 mm Mg(2+). However, we show here that this interaction was abolished in the presence of 25 microm EGTA. Adhesion of Glanzmann's thrombasthenic platelets, which lack the fibrinogen receptor alpha(IIb)beta(3), was also inhibited by micromolar EGTA. Mg(2+)-dependent adhesion of platelets was restored by the addition of 10 microm Ca(2+), but millimolar Ca(2+) was inhibitory. Binding of isolated alpha(2)beta(1) to GFOGER-GPP was 70% inhibited by 50 microm EGTA but, as with intact platelets, was fully restored by the addition of micromolar Ca(2+). 2 mm Ca(2+) did not inhibit binding of isolated alpha(2)beta(1) to collagen or to GFOGER-GPP. Binding of recombinant alpha(2) I-domain was not inhibited by EGTA, nor did millimolar Ca(2+) inhibit binding. Our data suggest that high affinity Ca(2+) binding to alpha(2)beta(1), outside the I-domain, is essential for adhesion to collagen. This is the first demonstration of a Ca(2+) requirement in alpha(2)beta(1) function.
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PMID:Micromolar Ca2+ concentrations are essential for Mg2+-dependent binding of collagen by the integrin alpha 2beta 1 in human platelets. 1082 98

During acute inflammatory processes, beta(2) and beta(1) integrins sequentially mediate leukocyte recruitment into extravascular tissues. We studied the influence of VLA-4 (very late antigen-4) (alpha(4)beta(1)) engagement on beta(2) integrin activation-dependent cell-to-cell adhesion. Ligation of VLA-4 by the soluble chimera fusion product vascular cell adhesion molecule-1 (VCAM-1)-Fc or by 2 anti-CD29 (beta(1) chain) monoclonal antibodies (mAb) rapidly induced adhesion of myelomonocytic cells (HL60, U937) to human umbilical vein endothelial cells (HUVECs). Cell adhesion was mediated via beta(2) integrin (LFA-1 and Mac-1) activation: induced adhesion to HUVECs was inhibited by blocking mAbs anti-CD18 (70%-90%), anti-CD11a (50%-60%), or anti-CD11b (60%-70%). Adhesion to immobilized ligands of beta(2) integrins (intercellular adhesion molecule-1 [ICAM-1], fibrinogen, keyhole limpet hemocyanin) as well as to ICAM-1-transfected Chinese hamster ovary cells, but not to ligands of beta(1) integrins (VCAM-1, fibronectin, laminin, and collagen), was augmented. VCAM-1-Fc binding provoked the expression of the activation-dependent epitope CBRM1/5 of Mac-1 on leukocytes. Clustering of VLA-4 through dimeric VCAM-1-Fc was required for beta(2) integrin activation and induction of cell adhesion, whereas monovalent VCAM-1 or Fab fragments of anti-beta(1) integrin mAb were ineffective. Activation of beta(2) integrins by alpha(4)beta(1) integrin ligation (VCAM-1-Fc or anti-beta(1) mAb) required the presence of urokinase receptor (uPAR) on leukocytic cells, because the removal of uPAR from the cell surface by phosphatidylinositol-specific phospholipase C reduced cell adhesion to less than 40%. Adhesion was reconstituted when soluble recombinant uPAR was allowed to reassociate with the cells. Finally, VLA-4 engagement by VCAM-1-Fc or anti-beta(1) integrin mAb induced uPAR-dependent adhesion to immobilized vitronectin as well. These results elucidate a novel activation pathway of beta(2) integrin-dependent cell-to-cell adhesion that requires alpha(4)beta(1) integrin ligation for initiation and uPAR as activation transducer. (Blood. 2000;96:506-513)
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PMID:VLA-4 (alpha(4)beta(1)) engagement defines a novel activation pathway for beta(2) integrin-dependent leukocyte adhesion involving the urokinase receptor. 1088 12

Compounds with potential antiplatelet activity can be used in the therapy of cardiovascular disorders. We investigated the effects of three different antioxidants with carcinostatic property: trans-resveratrol, Trolox a water-soluble analog of vitamin E, and inorganic selenocompounds (sodium selenite and selenate) on blood platelet adhesion to fibrinogen (Fg). Adhesion, the initial step of platelet activation, was estimated by the colorimetric method with BCA (bicinchoninic acid) solution in 96-well Fg-coated microtiter dishes. It was shown that resveratrol significantly inhibited adhesion of both thrombin- and ADP-activated platelets to Fg. After incubation of platelets for 30 min. at 37 degrees C with resveratrol at the concentration of 100 microg/ml above 40% inhibition of adhesion was achieved. The inhibition of platelet adhesion of Fg caused by Trolox was lower than by resveratrol and at higher concentration (1 mM) reached maximum 12%. We also demonstrated that neither sodium selenite nor selenate significantly altered platelet adhesion to Fg. We conclude that changed adhesion of blood platelets to Fg in the presence of resveratrol and Trolox, but not selenium may be the result of different antioxidative activities of tested compounds.
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PMID:Antioxidants with carcinostatic activity (resveratrol, vitamin E and selenium) in modulation of blood platelet adhesion. 1101 70

F(2)-Isoprostanes are generated from a cyclooxygenase-independent oxidative modification of arachidonic acid. They are present in atherosclerotic plaques and are platelet activators as well as potent vasoconstrictors. Polymorphonuclear neutrophils are major players in ischemia/reperfusion injury and in restenosis after PTCA. The effects of 8-isoprostaglandin (PG) F(2alpha) on very rapid beta(2)-integrin-dependent adhesion was evaluated in human neutrophils in vitro by use of purified integrin as ligand. 8-Iso-PGF(2alpha) (1 nmol/L to 20 micromol/L) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen but not to the endothelial ligand intercellular adhesion molecule-1. Pretreatment with anti-ss(2)-integrin subtypes showed activation of CD11b/CD18 and CD11c/CD18. Adhesion triggering was completely prevented by pertussis toxin. SQ29,548, a specific antagonist of thromboxane A2 receptor, also dose-dependently prevented 8-iso-PGF(2alpha)-triggered neutrophil adhesion. 8-Iso-PGF(2alpha) did not trigger adhesion in human monocytes and lymphocytes and did not induce neutrophil chemotaxis or activation of the oxygen free-radical-forming enzyme NADPH-oxidase. These data highlight the role of 8-iso-PGF(2alpha) as a specific activator of rapid neutrophil adhesion and suggest its involvement in the pathogenesis of ischemia/reperfusion injury and in restenosis after PTCA. The effect is transduced via activation of the receptor for thromboxane A2.
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PMID:8-Iso-PGF2 alpha induces beta 2-integrin-mediated rapid adhesion of human polymorphonuclear neutrophils: a link between oxidative stress and ischemia/reperfusion injury. 1114 33

Aged garlic extract (AGE) has been shown previously to have moderate cholesterol-lowering and blood pressure-reducing effects. We have now investigated whether platelet function, a potential risk factor for cardiovascular disease, can be inhibited by AGE administration. In a randomized, double-blind study of normal healthy individuals (n = 34), both men and women, the effect of AGE was evaluated in doses between 2.4 and 7.2 g/d vs. equal amounts of placebo. Platelet aggregation and adhesion were measured at 2-wk intervals throughout the study. Threshold concentrations for epinephrine and collagen increased moderately during AGE administration compared with the placebo and baseline periods. Only at the highest supplementation level did AGE show a slight increase in the threshold level of ADP-induced aggregation. Platelet adhesion to collagen, fibrinogen and von Willebrand factor was investigated by perfusing whole blood through a laminar flow chamber under controlled flow conditions. Adherence of platelets was inhibited by AGE in a dose-dependent manner when collagen was the adhesive surface perfused at low shear rates ( approximately 30 s(-1)). At high shear rates (1200 s(-1)), AGE also inhibited platelet adhesion to collagen but only at higher intake levels. Adhesion to von Willebrand factor was reduced only at 7.2 g/d AGE, but adherence to fibrinogen was potently inhibited at all levels of supplementation. Thus, AGE exerts selective inhibition on platelet aggregation and adhesion, platelet functions that may be important for the development of cardiovascular events such as myocardial infarction and ischemic stroke. We briefly review the effect of garlic preparations in general on cardiovascular risk factors and point out differences between AGE and other garlic preparations that we feel are important to explain the efficacy of AGE.
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PMID:Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. 1123 1

Adhesion of platelets to immobilized collagen induces the expression of anionic phospholipids, e.g. phosphatidylserine (PS), in the outer leaflet of the plasma membrane of these platelets. In contrast, of the platelets that adhere to immobilized fibrinogen only a small sub-population representing 10 +/- 3% of the total population of the fibrinogen-adherent platelets has exposed PS as probed by annexin V binding. Although the presence of PS is thought to be critical for thrombin generation at the platelet surface, no information is available about the effect of this differential PS exposure on the ability of adherent platelets to support thrombin generation. Perfusion of the fibrinogen- or collagen-adherent platelets with solutions containing factor Xa and prothrombin resulted in thrombin generation that i) increased linear during the first perfusion minutes, ii) was about two-fold faster at collagen-adherent than at fibrinogen-adherent platelets and iii) was for more than 98% restricted to the surface of the adherent platelets. It appeared that the lower thrombin generating capacity of fibrinogen-adherent platelets is not due to a lower overall surface density of PS, but is caused by lower amounts of platelet-bound factor Va. Firstly, in both cases thrombin generation could be completely attenuated with antibodies against human factor Va, and secondly, in the presence of an excess of exogenous plasma-derived factor Va similar initial rates of thrombin formation were measured for collagen- and fibrinogen-adherent platelets. Our findings suggest a unique role for immobilized collagen in maintaining haemostasis.
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PMID:Contribution of platelet-derived factor Va to thrombin generation on immobilized collagen- and fibrinogen-adherent platelets. 1168 47


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