Platelet adhesion at high shear rates: The roles of von Willebrand factor/GPIb and the β1 integrin α2β1

Abstract

We have previously described a monomeric rvWf fragment, Leu504-Lys728 that contains one disulfide bond linking Cys509-Cys695. This fragment, VCL, has previously been shown to inhibit vWf-ristocetin, asialo-vWf, and botrocetin-induced vWf binding and aggregation of platelets. VCL inhibited 50% of vWf binding to heparin, but it did not inhibit vWf binding to type I collagen. At a high shear force (2600 −1 sec), VCL inhibited platelet adhesion to the subendothelial surface of human umbilical arteries. The maximum inhibition of platelet adhesion was 83 ± 4% at a VCL concentration of 7.6μmol/L. Various monoclonal anti-Very Late Activation antigens (VLA) antibodies were added to the VCL and tested for their ability to enhance the inhibition of platelet adhesion at high shear forces. Of all of the VLA antibodies tested, only the anti-VLA-2 antibody (176D7) inhibited platelet aggregation in the absence of VCL and enhanced the inhibition of platelet adhesion in the presence of VCL. The VLA-2 antibody and VCL together inhibited 96 ± 4% of platelet adhesion at high shear forces.