Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia.
2005 (English)In: Blood, ISSN 0006-4971, Vol. 105, no 9, 3577-3582 p.Article in journal (Refereed) Published
Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein alpha (SIRPalpha) counteracts macrophage phagocytosis of CD47-expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRPalpha 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 SIRPalpha 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/SIRPalpha signaling is involved in regulating platelet phagocytosis in ITP, and that targeting SIRPalpha may be a new means of reducing platelet clearance in ITP.
Place, publisher, year, edition, pages
2005. Vol. 105, no 9, 3577-3582 p.
Animals, Antigens; CD/genetics/*physiology, Antigens; CD47, Antigens; Differentiation/physiology, Blood Platelets/*physiology, Cell Aging, Genotype, Homeostasis, Membrane Glycoproteins/physiology, Mice, Mice; Knockout, Neural Cell Adhesion Molecule L1/physiology, Phagocytosis, Platelet Transfusion, Purpura; Thrombocytopenic; Idiopathic/*blood/etiology, Receptors; Immunologic/physiology, Signal Transduction
IdentifiersURN: urn:nbn:se:umu:diva-12280DOI: doi:10.1182/blood-2004-08-2980PubMedID: 15665111OAI: oai:DiVA.org:umu-12280DiVA: diva2:151951