Identification of platelet glycoprotein IIb/IIIa as the major binding site for released platelet-von Willebrand factor.
We studied the effects(s) of two monoclonal antibodies, 6D1 and 10E5 (directed against platelet glycoprotein Ib [GPIb] and the GPIIb/IIIa complex, respectively), and purified human plasma fibrinogen on the binding of released platelet-von Willebrand factor (vWf) to the platelet surface. Neither of the monoclonal antibodies nor fibrinogen had any effect on the amount of platelet-vWf expressed on unstimulated platelets or on the amount expressed on platelets stimulated in the absence of extracellular Ca++. However, the antibody directed against GPIIb/IIIa inhibited 72% of the thrombin-induced increase in the platelet-vWf bound to the platelet surface when platelets were stimulated in the presence of 5 mmol/L Ca++. The antibody against GPIb did not inhibit the surface expression of platelet-vWf on stimulated platelets in the presence of Ca++. Purified normal human fibrinogen inhibited the surface binding of platelet-vWf to thrombin-stimulated platelets to a degree similar to that observed with the monoclonal antibody directed against the GPIIb/IIIa complex. These data indicate that platelet-vWf released from platelets binds primarily to the GPIIb/IIIa complex at or near the plasma fibrinogen binding site.
D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D001792:Blood Platelets / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000502:physiology*; D013917:Thrombin / Q000378:metabolism; D014841:von Willebrand Factor / Q000502:physiology*
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D008565:Membrane Proteins; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014841:von Willebrand Factor; D005340:Fibrinogen; D013917:Thrombin; D002118:Calcium