title: Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia.
abstract: 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.
authors.affiliation: Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Mattias
authors.initials: M
authors.lastname: Olsson
authors.forename: Pierre
authors.initials: P
authors.lastname: Bruhns
authors.forename: William A
authors.initials: WA
authors.lastname: Frazier
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Ravetch
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D051928:CD47 Antigen; D016922:Cellular Senescence; D005838:Genotype; D006706:Homeostasis; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000502:physiology; D010587:Phagocytosis; D017713:Platelet Transfusion; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000209:etiology; D011971:Receptors, Immunologic / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D008562:Membrane Glycoproteins; D039842:Neural Cell Adhesion Molecule L1; D011971:Receptors, Immunologic