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

The adhesion of platelets to purified laminin under flow conditions was investigated. Adhesion to laminin was strongly dependent on the presence of divalent cations. In the absence of cations platelet adhesion (8% coverage in 5 minutes) was maximal at a shear rate of 100/s and no adhesion could be detected at shear rates above 800/s. In the presence of 0.8 mmol/L Mg2+ and 2 mmol/L Ca2+ platelet adhesion reached its maximum (30% coverage) around 800/s. At 1,800/s platelets still adhered to purified laminin (coverage of 6%). Antibodies against the E8 domain of laminin and antibodies against the alpha 6 and beta 1 chains of platelet membrane glycoprotein very late activation antigen-6 (VLA-6), completely inhibited adhesion. No inhibition was found with antibodies against glycoprotein IIb:IIIa, against the alpha 2 chain of VLA-2, and against the alpha 5 chain of VLA-5. Fibronectin and von Willebrand factor were not involved in laminin-dependent adhesion. Anti-VLA-6 partly inhibited platelet adhesion to the extracellular matrix of endothelial cells at shear rates below 800/s. Preincubation of the matrices with antilaminin E8 antibodies did not influence the adhesion. These results show that purified laminin supports platelet adhesion and that the presence of VLA-6 is important for platelet adhesion under flow conditions. The protein in the matrix with which VLA-6 interacts is currently unknown.
 ...
PMID:Platelet adhesion to laminin: role of Ca2+ and Mg2+ ions, shear rate, and platelet membrane glycoproteins. 173 1

The role of fibrinogen in mediating platelet adhesion to polymers exposed to blood plasma was studied by comparison of the effect of plasma dilution on fibrinogen adsorption and platelet adhesion, and by the use of coagulation factor deficient plasmas. Polyetherurethane substrates were first preadsorbed with dilute plasma, then contacted with washed platelets suspended in a modified, apyrase containing Tyrode's buffer. Platelet adhesion was studied under static conditions in Multiwell dishes, and also under shearing conditions using a parallel plate perfusion chamber. Fibrinogen adsorption and platelet adhesion were measured using 125I radiolabeled baboon fibrinogen and 111In radiolabeled baboon platelets, respectively. Surfaces were characterized by electron spectroscopy for chemical analysis (ESCA). When fibrinogen adsorption to Biomer was measured after 2 h contact with a series of dilute plasma solutions under static conditions, a peak in adsorption was observed from 0.26% plasma, i.e., adsorption was greater from 0.26% plasma than from either more or less dilute plasma. A peak in subsequent platelet adhesion to the plasma preadsorbed surfaces, measured after 2 h static incubation with washed platelets, was also observed but occurred on Biomer preadsorbed with 1.0% plasma. When fibrinogen adsorption was measured after 5 min contact under shearing conditions, the fibrinogen adsorption peak occurred on surfaces that had been exposed to 1.0% plasma. A peak in platelet adhesion to these preadsorbed surfaces, measured after 5 min contact with the platelet suspensions under shearing conditions, was observed on Biomer preadsorbed with 0.1% plasma. Shifts between the positions of the peaks in protein adsorption and platelet adhesion occurred on other polymers tested as well. Platelet adhesion was almost completely inhibited when baboon and human plasmas lacking fibrinogen (i.e., serum, heat defibrinogenated plasma, and congenitally afibrinogenemic plasma) were used. Platelet adhesion was restored to near normal when exogenous fibrinogen was added to fibrinogen deficient plasmas. Adhesion was also inhibited completely when a monoclonal antibody directed against the glycoprotein IIb/IIIa complex was added to the platelet suspension. Platelet adhesion to surfaces preadsorbed to von Willebrand factor deficient plasma was the same as to surfaces preadsorbed with normal plasma. While it appears that surface bound fibrinogen does mediate the initial attachment of platelets to Biomer, the observation that the fibrinogen adsorption and platelet adhesion maxima do not coincide exactly also suggests that the degree of subsequent platelet adhesion is dictated not only by the amount of surface bound fibrinogen but also by its conformation.
 ...
PMID:Baboon fibrinogen adsorption and platelet adhesion to polymeric materials. 187 24

Interactions between human blood platelets and fibrin have been visualized by light microscopy, and quantitative details of the extent, rate and specificity of fibrin-platelet binding obtained by microfluorimetry. Adhesion of fluorescein-labelled fibrin to activated platelets yielded brightly fluorescent fibrin-platelet aggregates, which emitted light at an intensity 4-7-fold greater than that due to nonspecific association of fluorescein-fibrin with unstimulated fixed cells. The intensity of fluorescent light emitted from fibrin-platelet aggregates increased as a function of time, reaching a plateau after about 1 h under physiological buffer and temperature conditions. Two monoclonal antibodies directed against the glycoprotein IIb-IIIa complex, which have been shown to inhibit the binding of fibrinogen and soluble fibrin oligomers to ADP-stimulated platelets, were employed to further probe the specificity of this adhesive interaction. In contrast to the results with the soluble ligands, one of these antibodies (HP1-1D) was capable of fully inhibiting the attachment of fluorescent fibrin to ADP-activated cells while the other (AP-2) was much less effective.
 ...
PMID:An investigation of fibrin-platelet adhesive interactions by microfluorimetry. 309 1

Platelets adhere to vitronectin substrate following activation with physiological concentrations of thrombin. Adhesion of activated platelets to vitronectin substrate is dependent upon the presence of divalent cations, the amount of vitronectin, and the duration of adhesion assay. The adhesion of platelets is inhibited by synthetic peptides containing the sequence of Arg-Gly-Asp. In addition, monoclonal antibodies to glycoprotein IIb-IIIa complex inhibit the adhesion of activated platelets to vitronectin substrate in a dose-dependent manner. These studies suggest that the glycoprotein IIb-IIIa complex on activated platelets may interact with vitronectin substrate through the Arg-Gly-Asp mechanism. Since vitronectin is present in the subendothelial matrix, it might be involved in platelet-vessel wall interactions.
 ...
PMID:Interaction of thrombin-stimulated platelets with vitronectin (S-protein of complement) substrate: inhibition by a monoclonal antibody to glycoprotein IIb-IIIa complex. 323 53

Platelets adhere to fibronectin and vitronectin substrates following activation with physiological concentrations of thrombin. Adhesion of activated-platelets to either substrate is dependent upon the amount of fibronectin and vitronectin, and the duration of the adhesion assay. In this study, we showed that the Arg-Gly-Asp-containing peptides (including naturally occurring polypeptides, triflavin, trigramin and rhodostomin, synthetic peptides GRGDS, GRGDSPK, GRGDF, and GRGD and monoclonal antibodies, 7E3, 10E5 and AP2, raised against glycoprotein IIb/IIIa complex, inhibited the adhesion of activated-platelets to fibronectin and vitronectin-coated plates in a dose-dependent manner. In fibronectin-coated plates, GRGDF was shown to be much more efficient than GRGDS, GRGDSPK and GRGD at inhibiting the adhesion of activated-platelets to immobilized fibronectin. On the other hand, there were no marked differences in the abilities of these three peptides (GRGDF, GRGDS and GRGDSPK) to inhibit platelet adhesion to immobilized vitronectin. Furthermore, the RGD-containing venom peptide, triflavin was more effective than rhodostomin and trigramin at inhibiting the adhesion of activated-platelets to either substrates. The monoclonal antibodies raised against glycoprotein IIb/IIIa complex (i.e., 7E3, 10E5 and AP2) inhibited platelet adhesion to fibronectin and vitronectin in a similar dose-dependent manner. Interestingly, we found that 7E3 was more efficient than 10E5 and AP2 in this reaction. These studies suggest that the glycoprotein IIb/IIIa complex, present on activated-platelets, may interact with fibronectin and vitronectin substrates through the Arg-Gly-Asp-dependent mechanism. Since fibronectin and vitronectin are present in the subendothelial matrix, they may be involved in platelet-vessel wall interaction. The Arg-Gly-Asp containing peptide, especially triflavin, is an ideal therapeutic agent for inhibiting thrombus formation by interrupting platelet-platelet and platelet-subendothelium interactions.
 ...
PMID:Interaction of thrombin-activated platelets with extracellular matrices (fibronectin and vitronectin): comparison of the activity of Arg-Gly-Asp-containing venom peptides and monoclonal antibodies against glycoprotein IIb/IIIa complex. 912 Jul 75

Cross-reactivity with integrins other than glycoprotein IIb/IIIa (GP IIb/IIIa) is discussed as a potential reason for the overall clinical benefits of the GP IIb/IIIa-blocking antibody-fragment abciximab. We evaluated whether abciximab binds to the leukocyte integrin Mac-1, whether it inhibits binding of the distinct ligands and thereby may modulate inflammation, cell proliferation and coagulation. Binding of fluorescence-labelled abciximab to phorbolmyristate acetate-stimulated monocytes and to a monocytic cell line (THP-1) could be detected in flow cytometry. The binding of fibrinogen, the inactivated complement factor 3b (iC3b), and the coagulation factor X to Mac-1 could be inhibited by abciximab (10 microg/ml) in vitro. As a functional consequence, the conversion of factor X to factor Xa mediated by Mac-1, as detected by the chromogenic substrate SZ-2222, was impaired by abciximab. Adhesion of THP-1 cells to immobilized intercellular adhesion molecule 1 (ICAM-1) and to fibrinogen was reduced significantly by abciximab. Fibrinogen-mediated cell aggregation was also impaired. In conclusion, we describe binding of abciximab to Mac-1 on stimulated monocytes. Thereby, abciximab inhibits binding of the ligands fibrinogen, ICAM-1, iC3b and factor X. Furthermore, we demonstrated that Mac-1-dependent conversion from factor X to factor Xa is impaired by abciximab, arguing for the direct modulation of the coagulation cascade by abciximab. Overall, the inhibition of Mac-1 could provide additional clinical benefits of abciximab beyond the well-described blockade of GP IIb/IIIa.
 ...
PMID:The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2). 1243 77