AGONIST-ACTIVATED ALPHA-NU-BETA-3 ON PLATELETS AND LYMPHOCYTES BINDS TO THE MATRIX PROTEIN OSTEOPONTIN

The phosphorylated acidic glycoprotein osteopontin is present in the e xtracellular matrix of atherosclerotic plaques and the wall of injured but not normal arteries. To determine if osteopontin could serve as a substrate for platelet adhesion, we measured the adherence of resting and agonist-stimulated human platelets to immobilized recombinant hum an osteopontin. Agonist-stimulated but not resting platelets bound to osteopontin by a process that was mediated primarily by alpha v beta 3 . alpha v beta 3-mediated adherence occurred at physiologic concentrat ions of calcium and was inhibited by an alpha v beta 3-selective cycli c peptide. Assays using phorbol myristate acetate-stimulated transfect ed B lymphocytes expressing both alpha v beta 3 and alpha IIb beta 3 c onfirmed that activated alpha v beta 3 not activated alpha IIb beta 3 was responsible for the cellular adherence we measured. These studies indicate that alpha v beta 3 can reside on the cell surface in an inac tive state and can be converted to a ligand binding conformation by ce llular agonists. Moreover, they suggest that platelet adherence to ost eopontin mediated by activated alpha v beta 3 could play a role in anc horing platelets to disrupted atherosclerotic plaques and the walls of injured arteries. By inhibiting alpha v beta 3 function, it may be po ssible to inhibit platelet-mediated vascular occlusion with a minimal effect on primary hemostasis.