HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY 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 initiated by the interaction of the platelet membrane glycoprotein (GP) Ib-IX-V complex with its adhesive ligand, von Willebrand factor (vWF), in the subendothelial matrix or plasma. This interaction involves the A1 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 Iba antibodies—previously characterized for their effects on ristocetinand botrocetin-dependent vWF–GP Ib-IX-V interactions—was analyzed for their capacity to inhibit either the adhesion of Chinese hamster ovary cells expressing recombinant GP Iba to surface-associated vWF under hydrodynamic flow or shearstress–induced platelet aggregation. The combined results suggest that the sheardependent interactions between vWF and GP Iba closely correlate with ristocetinrather than botrocetin-dependent binding under static conditions and that certain anti-vWF monoclonal antibodies are able to selectively inhibit shear-dependent platelet aggregation. (Blood. 2001;97: 162-168)