Characterization of murine anti-glycoprotein ib monoclonal antibodies thatdifferentiate between shear-induced and ristocetin/botrocetin-induced glycoprotein Ib-von Willebrand Factor interaction

Platelet adhesion to vascular subendothelium under conditions of high shear stress is mediated by the platelet glycoprotein (GP) Ib-von Willebrand Fac tor (vWF) interaction. The aim of this study was to characterize the murine monoclonal antibodies (MoAbs) 27A10 and 28E6, both raised against purified GPlb. The MoAb 27A10 is a potent inhibitor of shear-induced platelet adhes ion to collagen type I in a flow chamber at shear rates of 1,300 and 2,700 s(-1). 20 mu g/ml of MoAb 27A10, furthermore, could completely block shear- induced aggregation in a modified Couette viscometer at shear rates of 1,00 0 and 4,000 s(-1). On the other hand, MoAb 27A10 had a negligible effect on botrocetin-induced GPlb-vWF binding and is only a poor inhibitor of the ri stocetin-dependent interaction. In contrast, MoAb 28E6 did abolish both the ristocetin- and botrocetin-induced GPlb-vWF binding, whereas it did not bl ock the shear-induced interaction. Thus, we identify here two anti-GPlb MoA bs 27A10 and 28E6 that either preferentially inhibit the shear-induced or t he ristocetin/botrocetin-induced platelet-VWF interaction. With these tools it should be possible to more clearly define the mechanisms by which plate lets bind to VWF in vivo. Copyright (C) 2000 S. Karger AG, Basel.