ANALYSIS OF THE INVOLVEMENT OF THE VON-WILLEBRAND-FACTOR GLYCOPROTEINIB INTERACTION IN PLATELET-ADHESION TO A COLLAGEN-COATED SURFACE UNDER FLOW CONDITIONS

The requisite initial reaction for in vivo thrombus formation in flowi ng blood is platelet adhesion to the exposed surface of the extracellu lar matrix, The contribution of von Willebrand factor (VWF) in plasma and glycoprotein (GP) Ib on the platelet membrane to platelet adhesion has been well-documented. We have recently developed a procedure (the ''flow adhesion assay'') for measuring platelet adhesion under flow c onditions that allowed us to characterize platelet adhesion to a colla gen-coated surface. Here, we apply our method to analyze platelet adhe sion to a vWF-coated surface to determine how this might differ from a dhesion to a collagen-coated surface. Platelet adhesion to the vWF-coa ted surface was monitored as the linear increase in the area occupied by adherent platelets. The fluorescence image showed that platelets ad hering to the vWF surface were mainly single platelets, and if any wer e present, the platelet aggregates were small, this being the primary difference from the adhesion to a collagen surface, where adherent pla telets were mostly in aggregates, The flow adhesion assay detected the movement of platelets on the vWF surface, suggesting the reversible b inding of vWF with platelets, The velocity of the platelets increased at higher shear rates or at lower vWF densities on the surface. Treatm ent of the vWF-coated surface with the aggregating agent botrocetin be fore initiation of blood flow increased platelet adhesion while dramat ically decreasing the velocity of platelet movement. The present obser vations on the adhesion of platelets to the vWF-pretreated collagen su rface and measurements of the velocity of platelets moving on the coll agen surface suggest that the first interaction on the collagen-coated surface is the binding of vWF molecules to the collagen surface. This small number of vWF molecules would serve to attract and slow platele ts flowing near the surface. This would facilitate the actual adhesion to the collagen surface that is mainly generated by the interaction b etween platelet collagen receptors, including GP Ia/IIa and GP VI, wit h collagen. (C) 1997 by The American Society of Hematology.