Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia
Platelet homeostasis is regulated by platelet expression of CD47 under normal conditions and in passive immune thrombocytopenia
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DOI：
10.1182/blood-2004-08-2980
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发表时间：
2005-05-01
期刊：
影响因子：
20.3
通讯作者：
Oldenborg, PA
中科院分区：
文献类型：
--
作者：
Olsson, M;Bruhns, P;Oldenborg, PA
靶细胞CD 47和抑制性巨噬细胞受体信号调节蛋白a（SIRPa）之间的相互作用抵消表达CD 47的宿主细胞的巨噬细胞吞噬作用。由于血小板也表达CD 47，我们询问抑制性CD 47/SIRP α信号传导是否调节免疫性血小板减少性紫癜（ITP）中正常的血小板周转和血小板清除。CD 47（-/-）小鼠出现轻度自发性血小板减少症，这不是由于P-选择素、CD 61或磷脂酰丝氨酸表达增加导致血小板半衰期缩短所致。相反，当输注到CD 47（+/+）受体中时，CD 47（-/-）血小板被迅速清除，而在非自身免疫条件下，CD 47（+/+）小鼠中CD 47（+/-）血小板具有几乎正常的半衰期。CD 47（-/-）小鼠对ITP的敏感性高于CD 47（+/+）小鼠。在体外，免疫球蛋白G（IgG）调理的CD 47（-/-）血小板的巨噬细胞吞噬作用显著高于同等调理的CD 47（+/+）血小板。然而，当SIRP α被阻断时，CD 47（+/+）血小板的吞噬作用增加到CD 47（-/-）血小板的水平。经调理的CD 47（+/-）血小板的吞噬功能高于CD 47（+/+）血小板，但低于CD 47（-/-）血小板，提示CD 47在该系统中存在基因剂量效应。总之，我们认为抑制性CD 47/SIRP α信号传导参与了ITP血小板吞噬的调节，靶向SIRP α可能是美国血液学会ITR（c）2005中降低血小板清除率的新方法。
Interaction between target cell CD47 and the inhibitory macrophage receptor signal regulatory protein a (SIRPa) counteracts macrophage phagocytosis of CD47-expressing host cells. As platelets also express CD47, we asked whether inhibitory CD47/SIRP alpha 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 alpha 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 alpha signaling is involved in regulating platelet phagocytosis in ITP, and that targeting SIRP alpha may be a new means of reducing platelet clearance in ITR (c) 2005 by The American Society of Hematology.