Distinct sequences of the glycoprotein Ib-binding domain of von Willebrand factor involved in shear induced platelet aggregation.

Shear-induced platelet aggregation (SIPA) requires von Willebrand factor (vWF) binding to the platelet receptors GPIb and alpha(IIb)beta(3). In order to determine the vWF sequences involved in SIPA at 4000/s, we studied the effect of three monoclonal antibodies (mabs) 724, 713 and 328 to the A1 domain of vWF, We found that mab 724 induced an enhanced SIPA via a Fc gamma-receptor independent mechanism. In contrast, mab 713 and mab 328 could inhibit SIPA by 52 and 91%, respectively, Based on distinct effects on SIPA, we can propose the following working model for the interaction between vWF and GPIb: mabs 713 and 328, which block SIPA, may recognize an epitope that is involved in binding to GPIb, whereas mab 724, which increases SIPA in the presence of vWF, may mimic the effect of botrocetin when binding to vWF, by inducing an active conformation of vWF, which may be more sensitive to high shear rate.