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Blood, 1 January 2001, Vol. 97, No. 1, pp. 162-168

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

Jing-Fei Dong, Michael C. Berndt, Alicia Schade, Larry V. McIntire, Robert K. Andrews, and José A. López

From the Departments of Medicine and Molecular and Human Genetics, Baylor College of Medicine, and the Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX; and the Hazel and Pip Appel Vascular Biology Laboratory, Baker Medical Research Institute, Melbourne, Australia.

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 Ibalpha (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 Ibalpha antibodies---previously characterized for their effects on ristocetin- and 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 Ibalpha to surface-associated vWF under hydrodynamic flow or shear-stress-induced platelet aggregation. The combined results suggest that the shear-dependent interactions between vWF and GP Ibalpha closely correlate with ristocetin- rather than botrocetin-dependent binding under static conditions and that certain anti-vWF monoclonal antibodies are able to selectively inhibit shear-dependent platelet aggregation.

© 2001 by The American Society of Hematology.
 

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