Integrin α2β1-independent activation of platelets by simple collagen-like peptides: Collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for α2β1-independent platelet reactivity

Abstract

The platelet reactivities of two simple collagen-like synthetic peptides, Gly-Lys-Hyp-(Gly-Pro-Hyp)10-Gly-Lys-Hyp- and Gly-Cys-Hyp-(Gly-Pro-Hyp)10-Gly-Cys-Hyp- were investigated. Both peptides adopted a stable triple-helical conformation in solution. Following cross-linking, both peptides proved to be highly platelet-aggregatory, more active than collagen fibres, inducing aggregation at concentrations as low as 20 ng/ml. These peptides formed microaggregates in solution, and crosslinking was thought to stabilize these structures, allowing expression of their platelet reactivity at 37°C. Like collagen fibres, the peptides caused platelet secretion and release of arachidonate from platelet membrane lipids as well as activation of integrin αIIbβ3 culminating in aggregation. Monoclonal antibodies directed against the integrin α2β1 failed to prevent aggregation, release of arachidonate or platelet adhesion to the peptides. Our results indicate that collagen can activate platelets by a mechanism that is independent of integrin α2β1 and for which collagen tertiary and quaternary structures are sufficient alone for activity without the involvement of highly specific cell-recognition sequences.