3 years ago

Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells [Medical Sciences]

Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells [Medical Sciences]
Jianhua Song, Jianxin Fu, Yun Li, Jamey D. Marth, Zhenghui Liu, Yuji Kondo, Bojing Shao, Xia Bai, J. Michael McDaniel, Changgeng Ruan, Roberto Sonon, Yannan Qin, Tadayuki Yago, Christopher Hoover, Rodger P. McEver, Lijun Xia, Parastoo Azadi, Yun Ling, Samuel McGee

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 α-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.

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