期刊
BLOOD
卷 128, 期 6, 页码 862-865出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2016-05-714378
关键词
-
类别
资金
- Deutsche Forschungsgemeinschaft [SFB 688]
- Rudolf Virchow Center
The activating platelet collagen receptor glycoprotein VI (GPVI) is a promising antithrombotic target because of its central role in arterial thrombosis and its minor relevance for normal hemostasis. The receptor can be specifically targeted by antibodies and irreversibly downregulated in circulating platelets in vivo, resulting in long-term antithrombotic protection in mice. This GPVI immunodepletion predominantly occurs through ectodomain shedding, which is accompanied by a transient drop in peripheral platelet counts. Mechanistic studies on this targeted GPVI loss have been hampered because it cannot be reproduced in isolated platelets in vitro. Here we show that both the transient thrombocytopenia and GPVI ectodomain shedding depend on the Fc portion of the anti-GPVI antibody and its interaction with the inhibitory Fc gamma receptor (Fc gamma R)IIB. In wild-type, but not Fcgr2b(-/-) mice, anti-GPVI-opsonized platelets became transiently trapped in the liver followed by the appearance of the soluble GPVI ectodomain in the plasma. Depletion of Kupffer cells neither affected anti-GPVI-induced platelet accumulation nor GPVI shedding, demonstrating that the other major Fc gamma RIIB-expressing cell type, liver sinusoidal endothelial cells, is required for both processes to occur. These results reveal a novel and unexpected function of hepatic Fc gamma RIIB in the targeted downregulation of GPVI in vivo. (Blood. 2016;128(6):862-865)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据