INTEGRIN ALPHA-2-BETA-1-INDEPENDENT ACTIVATION OF PLATELETS BY SIMPLECOLLAGEN-LIKE PEPTIDES - COLLAGEN TERTIARY (TRIPLE-HELICAL) AND QUATERNARY (POLYMERIC) STRUCTURES ARE SUFFICIENT ALONE FOR ALPHA-2-BETA-1-INDEPENDENT PLATELET REACTIVITY

The platelet reactivities of two simple collagen-like synthetic peptid es, Gly-Lys-Hyp-(Gly-Pro-Hyp)(10)-Gly-Lys-Hyp-Gly and Gly-Cys-Hyp-(Gly -Pro-Hyp)(10)-Gly-Cys-Hyp-Gly, were investigated. Both peptides adopte d a stable triple-helical conformation in solution. Following cross-li nking, both peptides proved to be highly platelet-aggregatory, more ac tive than collagen fibres, inducing aggregation at concentrations as l ow as 20 ng/ml. These peptides formed microaggregates in solution, and crosslinking was thought to stabilize these structures, allowing expr ession of their platelet reactivity at 37 degrees C. Like collagen fib res, the peptides caused platelet secretion and release of arachidonat e from platelet membrane lipids as well as activation of integrin alph a IIb beta 3 culminating in aggregation. Monoclonal antibodies directe d against the integrin alpha 2 beta 1 failed to prevent aggregation, r elease of arachidonate or platelet adhesion to the peptides. Our resul ts indicate that collagen can activate platelets by a mechanism that i s independent of integrin alpha 2 beta 1 and for which collagen tertia ry and quaternary structures are sufficient alone for activity without the involvement of highly specific cell-recognition sequences.