PEPTIDE LSARLAF ACTIVATES ALPHA(IIIB)BETA(3) ON RESTING PLATELETS ANDCAUSES RESTING PLATELET AGGREGATE FORMATION WITHOUT PLATELET SHAPE CHANGE

Adhesion of resting platelets to fibrinogen was enhanced by a peptide which was designed to bind near the presumptive fibrinogen gamma-chain binding site of the alpha subunit of the integrin alpha(IIb)beta(3). This peptide, but not a scrambled control peptide, induced adhesion of resting platelets to fibronectin, vitronectin, von Willebrand factor, and monovalent (lacks one functional gamma-chain) fibrinogen. Resting platelets not treated with the agonist peptide did not adhere to thes e ligands. Agonist peptide induced adhesion of resting platelets to Fg was not secretion dependent and was inhibited by the monoclonal antib ody 7E3. The agonist peptide caused aggregation of resting platelets o n resting platelets adherent to immobilized Fg without causing platele t shape change. Therefore, the agonist peptide may activate alpha(IIb) beta(3) by directly inducing a conformation change in the receptor on resting platelets. (C) 1998 Elsevier Science Ltd.