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Li, Yun; Fu, Jianxin; Ling, Yun; Yago, Tadayuki; McDaniel, J. Michael; Song, Jianhua; Bai, Xia; Kondo, Yuji; Qin, Yannan; Hoover, Christopher; McGee, Samuel; Shao, Bojing; Liu, Zhenghui; Sonon, Roberto; Azadi, Parastoo; Marth, Jamey D.; McEver, Rodger P.; Ruan, Changgeng; Xia, Lijun
Proceedings of the National Academy of Sciences - PNAS, 08/2017, Letnik: 114, Številka: 31Journal Article
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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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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