Evaluation of the role of platelet integrins in fibronectin-dependent spreading and adhesion

Background: Recent studies have shown that platelet adhesion and subsequent aggregation can occur in vivo in the absence of the two principal platelets adhesive ligands, von Willebrand factor and fibrinogen. These results highlight a possible role for fibronectin in supporting thrombus formation. Objective and methods: To evaluate the platelet integrins and subsequent activation pathways associated with fibronectin-dependent platelet adhesion utilizing both human and murine platelets. Results: Platelets can adhere to fibronectin via the integrin α_IIbβ₃, leading to formation of lamellipodia. This is mediated through an interaction with the tenth type III domain in fibronectin. Spreading on fibronectin promotes α_IIbβ₃-mediated Ca²⁺ mobilization and tyrosine phosphorylation of focal adhesion kinase and phospholipase C γ2. In contrast, studies with blocking antibodies and α_IIb^-/- mice demonstrate that α₅β₁ and α_vβ₃ support adhesion and promote formation of filopodia but not lamellipodia or tyrosine phosphorylation of these proteins. Further, neither α₅β₁ nor α_vβ₃ is able to induce formation of lamellipodia in the presence of platelets agonists, such as collagen-related-peptide (CR-P). Conclusions: These observations demonstrate that integrins α₅β₁ and α_vβ₃ support platelet adhesion and the generation of filopodia but that, in contrast to the integrin α_IIbβ₃, are unable to promote formation of lamellipodia.