Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells
Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells
复制标题
O-聚糖上的唾液酸化可保护血小板免于被肝库普弗细胞清除
DOI：
10.1073/pnas.1707662114
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发表时间：
2017-08-01
影响因子：
11.1
通讯作者：
Xia, Lijun
中科院分区：
文献类型：
--
作者：
Li, Yun;Fu, Jianxin;Xia, Lijun
大多数血小板膜蛋白被粘液型核心1-衍生糖链(O-糖链)修饰。然而，O-葡聚糖在清除血小板中的生物学重要性尚不清楚。在这里，我们产生了造血细胞特异性O-糖链丢失的小鼠(HC C1galt1(-/-))。这些小鼠缺乏血小板上的O-糖链，并表现出外周血小板数量的减少。与野生型血小板相比，来自HC C1galt1(-/-)小鼠的血小板显示出α-2，3-连接唾液酸水平的降低和在肝脏中积累的增加。在缺乏肝脏去唾液酸糖蛋白受体[Ashwell-Morell受体(AMR)]的小鼠中，HC C1galt1(-/-)血小板的优先聚集减少。然而，我们发现Kupffer细胞是肝脏中吞噬HC C1galt1(-/-)血小板的主要细胞。我们的结果表明，肝脏AMR通过其C型凝集素受体CLEC4F促进Kupffer细胞对所需的和/或HC的C1galt1(-/-)血小板的优先黏附和吞噬。这些发现提供了对核心1 O-糖基化在其在肝脏清除中的重要作用的洞察。
Most platelet membrane proteins are modified by mucin-type core 1-derived glycans (O-glycans). However, the biological importance of O-glycans in platelet clearance is unclear. Here, we generated mice with a hematopoietic cell-specific loss of O-glycans (HC C1galt1(-/-)). These mice lack O-glycans on platelets and exhibit reduced peripheral platelet numbers. Platelets from HC C1galt1(-/-) mice show reduced levels of alpha-2,3-linked sialic acids and increased accumulation in the liver relative to wild-type platelets. The preferential accumulation of HC C1galt1(-/-) platelets in the liver was reduced in mice lacking the hepatic asialoglycoprotein receptor [Ashwell-Morell receptor (AMR)]. However, we found that Kupffer cells are the primary cells phagocytosing HC C1galt1(-/-) platelets in the liver. Our results demonstrate that hepatic AMR promotes preferential adherence to and phagocytosis of desialylated and/or HC C1galt1(-/-) platelets by the Kupffer cell through its C-type lectin receptor CLEC4F. These findings provide insights into an essential role for core 1 O-glycosylation of platelets in their clearance in the liver.