Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf) antibody GUR76-23 which inhibits vWf interaction with α(IIb)β₃ but not α(v)β₃ integrin

von Willebrand factor (vWf) is known to interact with the two β₃ integrins, α(IIb)β₃ and α(v)β₃, in an RGD-dependent manner. We characterized a novel murine monoclonal antibody to human vWf, GUR76-23, which recognized a site within the carboxy-terminal half of the molecule containing the RGD sequence. This antibody inhibited high shear-induced platelet aggregation and blocked adhesion of ADP plus epinephrine-stimulated platelets to vWf, indicating that it interferes with the interaction with α(IIb)β₃. Unlike antibodies against the RGD site, however, the antibody was without effect on adhesion of cultured human umbilical vein endothelial cells to vWf, a phenomenon known to involve the interaction with α(v)β₃. GUR76-23 binding was not displaced by anti-RGD antibodies. These results suggest that the adhesive interaction of vWf with these two β₃ integrins may be differentially modulated by a site(s) other than the common RGD module.