DIRECT DEMONSTRATION OF RADIOLABELED VON-WILLEBRAND-FACTOR BINDING TOPLATELET GLYCOPROTEIN IB AND IIB-IIIA IN THE PRESENCE OF SHEAR-STRESS

In this study it is demonstrated for the first time that shear stress induces the binding of exogenous von Willebrand factor (vWF) multimers to platelets. The vWF preparations used were: I-125-vWF purified from human cryoprecipitate (and including all vWF multimers present in nor mal plasma); and S-35-cysteine-vWF secreted by human umbilical vein en dothelial cells (HUVECs) (and containing unusually large vWF forms, as well as all plasma-type vWF multimers). Direct shear-induced binding to washed platelets (300-360 x 10(3)/mu l) of radiolabeled vWF was max imum at 60-120 dynes/cm(2) evaluated at 30 sec and was in extent about one-quarter of the binding stimulated by ristocetin after 3 min of in cubation. The shear-induced binding of only a small percentage of adde d radiolabeled vWF was sufficient to initiate aggregation. Radiolabele d vWF attached to both glycoprotein (GP) Ib and GPIIb-IIIa receptors i n the shear field, with complete inhibition of binding occurring with simultaneous blockade of both receptors. Binding was potentiated by AD P released from sheared platelets.