Thrombospondin-1 acts via IAP/CD47 to synergize with collagen in alpha 2 beta 1-mediated platelet activation

Integrin-associated protein (IAP; or CD47) is a receptor for the cell bindi ng domain (CBD) of thrombospondin-1 (TS1). In platelets, IAP associates wit h and regulates the function of alpha llb beta 3 integrin (Chung et at, J B iol Chem 272:14740, 1997). We test here the possibility that CD47 may also modulate the function of platelet integrin alpha 2 beta 1, a collagen recep tor. The CD47 agonist peptide, 4N1K (KRFYVVMWKK), derived from the CBD, syn ergizes with soluble collagen in aggregating platelet-rich plasma. 4N1K and intact TS1 also induce the aggregation of washed, unstirred platelets on i mmobilized collagen with a rapid increase in tyrosine phosphorylation. The effects of TS1 and 4N1K on platelet aggregation are absolutely dependent on IAP, as shown by the use of platelets from IAP(-/-) mice. Prostaglandin E1 (PGE1) prevents 4N1K-dependent aggregation on immobilized collagen but doe s not inhibit the 4N1K peptide stimulation of alpha 2 beta 1-dependent plat elet spreading. Finally, a detergent-stable, physical association of IAP an d alpha 2 beta 1 integrin is detected by coimmunoprecipitation. These resul ts imply a role for IAP and TS1 in the early activation of platelets upon a dhesion to collagen. (C) 1999 by The American Society of Hematology.