Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia.
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.
Olsson
Mattias
M
Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, SE-901 87 Umeå, Sweden.
Bruhns
Pierre
P
Frazier
William A
WA
Ravetch
Jeffrey V
JV
Oldenborg
Per-Arne
PA
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
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