The dualistic mechanisms of platelet adhesion to von Willebrand factor substrates.
von Willebrand factor (vWf) which serves as a necessary factor for platelet adhesion to damaged vascular subendothelium can bind to the platelet surface via two distinct receptors. Ristocetin promotes the binding of vWf to platelet membrane glycoprotein lb, whereas platelet activation by thrombin supports binding to the glycoprotein IIb/IIIa complex. Platelet adhesion to vWf substrates mediated by these two mechanisms has been compared. Both mechanisms supported similar rates of adhesion to the substrates. Whereas adhesion via the ristocetin-dependent mechanism did not require divalent cations, adhesion mediated by the thrombin-dependent mechanism required the presence of divalent cations. Modification of vWf amino groups markedly impaired the ability of the protein to support ristocetin-dependent adhesion but did not alter its ability to support thrombin-enhanced adhesion. Reduction and carboxymethylation nearly abolished the ability of vWf to support adhesion via the ristocetin-dependent mechanism, but did not substantially impair its ability to support thrombin-enhanced adhesion. Short synthetic peptides containing the sequence Arg-Gly-Asp-Ser effectively inhibited thrombin-dependent platelet adhesion to vWf substrates but had no effect on ristocetin-dependent adhesion. Substrates composed of synthetic peptides containing the Arg-Gly-Asp-Ser sequence supported thrombin-dependent adhesion but did not support ristocetin-dependent adhesion. Scanning electron microscopic examination revealed that platelets adherent via the ristocetin-dependent mechanism almost uniformly adopted a flattened and fully spread appearance. In contrast, the thrombin-enhanced mechanism of adhesion supported only a limited degree of platelet spreading on the vWf substrate.
D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008745:Methylation; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction; D010973:Platelet Adhesiveness / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000502:physiology; D013917:Thrombin / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D014841:von Willebrand Factor / Q000502:physiology*
D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D014302:Trinitrobenzenesulfonic Acid; C046617:arginyl-glycyl-aspartyl-serine; D013917:Thrombin; D002118:Calcium