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Blood, Vol. 94 No. 2 (July 15), 1999:
pp. 642-648
Thrombospondin-1 Acts Via IAP/CD47 to Synergize With Collagen in
2 1-Mediated Platelet Activation
Jun Chung,
Xue-Qing Wang,
Frederik P. Lindberg, and
William A. Frazier
From the Department of Biochemistry and Molecular Biophysics and
Internal Medicine, Washington University School of Medicine, St Louis,
MO.
Integrin-associated protein (IAP; or CD47) is a receptor for the
cell binding domain (CBD) of thrombospondin-1 (TS1). In platelets, IAP
associates with and regulates the function of IIb 3 integrin (Chung et al, J Biol Chem 272:14740, 1997). We test here the
possibility that CD47 may also modulate the function of platelet
integrin 2 1, a collagen receptor. The CD47 agonist peptide, 4N1K
(KRFYVVMWKK), derived from the CBD, synergizes with soluble collagen in
aggregating platelet-rich plasma. 4N1K and intact TS1 also induce the
aggregation of washed, unstirred platelets on immobilized 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 does not inhibit the 4N1K peptide stimulation
of 2 1-dependent platelet spreading. Finally, a detergent-stable, physical association of IAP and 2 1 integrin is detected by
coimmunoprecipitation. These results imply a role for IAP and TS1 in
the early activation of platelets upon adhesion to collagen.

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