Contribution of distinct platelet integrins to binding, unfolding, and assembly of fibronectin

Abstract

Abstract Fibronectin (FN) fibrillogenesis depends on the binding of FN to cellular receptors and subsequent unfolding of bound FN. Integrins αIIbβ3, αvβ3, and α5β1 are known to assemble FN fibrils on platelets. In our study, we examined the contribution of these integrins to FN binding, unfolding, and assembly on platelets in suspension and adherent platelets in the presence or absence of agonists. Phorbol 12-myristate 13-acetate (PMA), but not adenosine diphosphate (ADP), induced binding of FN to platelets in suspension. In contrast, adherent platelets were able to deposit FN on their surfaces in the absence of agonists. β3 integrins had a major impact on the interaction of FN on platelets. αvβ3 showed a similar contribution to the binding of FN as αIIbβ3 on PMA-stimulated platelets in suspension but had a lesser contribution to unfolding and deposition of FN on adherent platelets. α5β1 also participated in the interaction of FN with platelets by mediating the unfolding and assembly of FN, but to a lesser extent than β3 integrins. None of the distinct antibodies directed against one of the three integrins caused a complete inhibition of binding, unfolding, and assembly of FN by platelets. Thus, it is likely that αIIbβ3, αvβ3, and α5β1 or another still unknown receptor can be substituted.