How vitronectin binds to activated glycoprotein IIb-IIIa complex and its function in platelet aggregation.
Vitronectin, which is present in both plasma and extracellular matrix, inhibits the complement cascade and promotes the growth and attachment of cells in vitro. Like other adhesive proteins such as fibrinogen, von Willebrand factor, and fibronectin, vitronectin contains the sequence Arg-Gly-Asp and binds to some members of the family of receptors called integrins. Platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa) is well known as a member of integrins that bind to vitronectin as well as to fibrinogen, von Willebrand factor, and fibronectin. The interaction of vitronectin with GPIIb-IIIa was studied. Vitronectin bound to thrombin-stimulated platelets in a calcium-dependent, specific, and saturable manner with a molecular weight of 290 nmol/L and 9,100 sites per platelet. The binding was inhibited by the other adhesive proteins with IC50s of 0.078-0.15 mumol/L. The binding also was inhibited by the tetrapeptide Arg-Gly-Asp-Ser and the monoclonal antibody to GPIIb-IIIa (LJ-CP8). Vitronectin inhibited thrombin-induced platelet aggregation in a dose-dependent manner and fibrinogen enhanced platelet aggregation. These results suggest that vitronectin might modulate platelet aggregates by interfering with the interaction of fibrinogen with thrombin-activated GPIIb-IIIa.
Mohri
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First Department of Internal Medicine, School of Medicine, Yokohama City University, Japan.
Ohkubo
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T
D000596:Amino Acids / Q000032:analysis; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D019096:Vitronectin
D000596:Amino Acids; D000911:Antibodies, Monoclonal; D005353:Fibronectins; D006023:Glycoproteins; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; D019096:Vitronectin; C046617:arginyl-glycyl-aspartyl-serine; D013917:Thrombin