SELECTIVE INDUCTION OF A GLYCOPROTEIN IIIA LIGAND-INDUCED BINDING-SITE BY FIBRINOGEN AND VON-WILLEBRAND-FACTOR

Ligand-induced binding sites (LIBS) are neoantigenic regions of glycop rotein (GP)IIb-IIIa that are exposed upon interaction of the receptor with the ligand fibrinogen or the ligand recognition sequence (RGDS). LIBS have been suggested to contribute to postreceptor occupancy event s such as full-scale platelet aggregation, adhesion to collagen, and c lot retraction. This study examined the induction requirements of a GP IIIa LIBS with regard to ligand specificity. Through the use of the an ti-LIBS D3, we report that this complex-activating antibody induces fi brinogen- and von Willebrand factor-binding to GPIIb-IIIa on intact pl atelets. Bound ligand was detected by flow cytometric analysis and pla telet aggregation assays. These bound ligands increased the number of D3-binding sites and altered the affinity of D3 for GPIIb-IIIa on plat elets. In contrast, activation of platelet GPIIb-IIIa by D3 did not in crease the binding of another RGD-containing ligand, vitronectin. Furt hermore, bound vitronectin on thrombin-stimulated platelets did not ca use the expression of the D3 LIBS epitope. We conclude direct activati on of GPIIb-IIIa in the absence of platelet activation results in sele ctive ligand interaction and that D3 LIBS induction requires the bindi ng of the multivalent ligands, fibrinogen or von Willebrand factor. Th us, the region of GPIIIa recognized by D3 may be an important regulato ry domain in ligand-receptor interactions that directly mediate platel et aggregation, (C) 1996 by The American Society of Hematology.