Vitronectin binds to activated human platelets and plays a role in platelet aggregation.
Vitronectin (Vn) is a multifunctional 75-kD glycoprotein that is present in plasma and the extracellular matrix. Vn functions as a complement regulatory protein in plasma, and promotes the growth and attachment of cells in tissue culture. Recent cDNA cloning reveals that like other adhesive proteins, Vn contains the sequence Arg-Gly-Asp and binds to some members of the integrin class of adhesive membrane receptors. In liposomes, the platelet membrane glycoprotein complex IIb/IIIa binds Vn, as well as fibrinogen, von Willebrand factor, and fibronectin. We examined the binding of purified Vn to resting and stimulated human platelets. Vn bound to thrombin-stimulated platelets in a calcium-dependent, specific, and saturable manner with a Kd of 320 nM and 8,000 sites per platelet. Epinephrine or ADP stimulation led to specific binding with KdS of 93 and 116 nM, respectively. Binding was inhibited by the tetrapeptide Arg-Gly-Asp-Ser and by monoclonal and polyclonal antibodies to GPIIb/IIIa. Endogenous platelet Vn stores were identified in immunoblots of gel-filtered platelets and the surface expression of endogenous platelet Vn was thrombin inducible. Monoclonal as well as polyclonal antibodies to Vn inhibited platelet aggregation, suggesting that Vn plays a role in the formation of stable platelet aggregates.
Division of Rheumatic Diseases and Immunology, New York Medical College, Valhalla 10595.
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Podack
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D001798:Blood Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D007122:Immunoelectrophoresis; D007700:Kinetics; D008970:Molecular Weight; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D011971:Receptors, Immunologic / Q000378:metabolism*; D019030:Receptors, Vitronectin; D019096:Vitronectin
D000906:Antibodies; D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D006023:Glycoproteins; D010975:Platelet Aggregation Inhibitors; D011971:Receptors, Immunologic; D019030:Receptors, Vitronectin; D019096:Vitronectin