Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions

Under conditions of high shear stress, both hemostasis and thrombosis are i nitiated by the interaction of the platelet membrane glycoprotein (GP) Ib-I X-V complex with its adhesive ligand, von Willebrand factor (VWF), in the s ubendothelial matrix or plasma. This interaction involves the Al domain of vWF and the N-terminal extracellular region of GP Iba (His-1-Glu-282), and it can also be induced under static conditions by the modulators ristocetin and botrocetin, In this study, a panel of anti-vWF and anti-GP Ib alpha an tibodies-previously characterized for their effects on ristocetin- and botr ocetin-dependent vWF-GP Ib-IX-V interactions-was analyzed for their capacit y to inhibit either the adhesion of Chinese hamster ovary cells expressing recombinant GP Iba to surface-associated vWF under hydrodynamic flow or she ar-stress-induced platelet aggregation. The combined results suggest that t he shear-dependent interactions between vWF and GP Ib alpha closely correla te with ristocetin-rather than botrocetin-dependent binding under static co nditions and that certain anti-vWF monoclonal antibodies are able to select ively inhibit sheer-dependent platelet aggregation. The combined results su ggest that the shear-dependent interactions between vWF and GP Ib alpha clo sely correlate with ristocetin-rather than botrocetin-dependent binding und er static conditions and that certain anti-vWF monoclonal antibodies are ab le to selectively inhibit sheer-dependent platelet aggregation. (C) 2001 by The American Society of Hematology.