Binding of human von Willebrand factor to collagen and to collagen-stimulated platelets.
Binding of von Willebrand factor (vWF) to collagen and to "collagen-stimulated platelets" was studied. Purified human iodine 125-labeled vWF binds to collagen. Binding was rapid, dependent on collagen and vWF concentration, independent of divalent ion concentration, and inhibited by unlabeled vWF as well as by high concentrations of fibronectin and fibrinogen. It was blocked by six monoclonal antibodies (MAbs) to human vWF (B200 through B205). Conversely, binding of 125I-vWF to platelets in the presence of collagen (collagen-treated platelets) was time dependent, saturable, and dependent on collagen, vWF, and divalent ion concentration. It was also inhibited by unlabeled vWF, fibronectin, or fibrinogen as well as by MAbs to vWF B200 through B205. In addition, binding of vWF to collagen-treated platelets was blocked by MAb to vWF 9 previously shown to inhibit binding of vWF to glycoprotein (GP) IIb-IIIa as well as by a MAb to GPIIb-IIIa. This binding was also strikingly decreased with use of patient platelets deficient in either GPIIb-IIIa or GPIa, whereas it was normal in the presence of a MAb to GPIb or when testing patient platelets deficient in GPIb. In conclusion, binding of vWF to platelets in the presence of collagen appeared to be a three-step phenomenon, including: binding of vWF to collagen; interaction of collagen with its receptor on the platelet membrane (GPIa ?), leading to activation of platelets and exposure of GPIIb-IIIa; and binding of vWF to GPIIb-IIIa.
D000911:Antibodies, Monoclonal; D001606:Bernard-Soulier Syndrome / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D003094:Collagen / Q000378:metabolism* / Q000494:pharmacology; D006023:Glycoproteins / Q000097:blood / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology; D013915:Thrombasthenia / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D001798:Blood Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D014841:von Willebrand Factor; D003094:Collagen