CHARACTERIZATION OF THE NOVEL MURINE MONOCLONAL ANTI-VON-WILLEBRAND FACTOR (VWF) ANTIBODY GUR76-23 WHICH INHIBITS VWF INTERACTION WITH ALPHA(IIB)BETA(3) BUT NOT ALPHA-V-BETA(3) INTEGRIN

von Willebrand factor (vWf) is known to interact with the two beta(3) integrins, alpha(IIb)beta(3) and alpha(v) beta(3), 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 hal f of the molecule containing the RGD sequence. This antibody inhibited high shear-induced platelet aggregation and blocked adhesion of ADP p lus epinephrine-stimulated platelets to vWf, indicating that it interf eres with the interaction with alpha(IIb)beta(3). Unlike antibodies ag ainst the RGD site, however, the antibody was without effect on adhesi on of cultured human umbilical vein endothelial cells to vWf, a phenom enon known to involve the interaction with alpha(v) beta(3). GUR76-23 binding was not displaced by anti-RGD antibodies. These results sugges t that the adhesive interaction of vWf with these two beta(3) integrin s may be differentially modulated by a site(s) other than the common R GD module. (C) 1997 Academic Press.