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 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.
Dong
J F
JF
Departments of Medicine and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. jfdong@bcm.tmc.edu
Berndt
M C
MC
Schade
A
A
McIntire
L V
LV
Andrews
R K
RK
López
J A
JA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001809:Blood Viscosity; D003435:Crotalid Venoms / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000939:Epitopes; D006801:Humans; D008958:Models, Molecular; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D012310:Ristocetin / Q000494:pharmacology*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003435:Crotalid Venoms; D000939:Epitopes; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor; D012310:Ristocetin; C030961:botrocetin