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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3577-3582.
Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2004-08-2980.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia
Mattias Olsson,
Pierre Bruhns,
William A. Frazier,
Jeffrey V. Ravetch, and
Per-Arne Oldenborg
From the Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, Sweden; the Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY; and the Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St Louis, MO.
Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein  (SIRP) counteracts macrophage phagocytosis of CD47-expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRP signaling regulates normal platelet turnover and clearance of platelets in immune thrombocytopenic purpura (ITP). CD47-/- mice had a mild spontaneous thrombocytopenia, which was not due to a decreased platelet half-life as a result of increased expression of P-selectin, CD61, or phosphatidylserine. In contrast, CD47-/- platelets were rapidly cleared when transfused into CD47+/+ recipients, whereas CD47+/- platelets had a nearly normal half-life in CD47+/+ mice under nonautoimmune conditions. CD47-/- mice were more sensitive to ITP, as compared with CD47+/+ mice. In vitro, macrophage phagocytosis of immunoglobulin G (IgG)–opsonized CD47-/- platelets was significantly higher than that for equally opsonized CD47+/+ platelets. However, when SIRP was blocked, phagocytosis of CD47+/+ platelets increased to the level of CD47-/- platelets. Phagocytosis of opsonized CD47+/- platelets was higher than that for CD47+/+ platelets, but lower than that for CD47-/- platelets, suggesting a gene-dose effect of CD47 in this system. In conclusion, we suggest that inhibitory CD47/SIRP signaling is involved in regulating platelet phagocytosis in ITP, and that targeting SIRP may be a new means of reducing platelet clearance in ITP.
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