| Literature DB >> 28716912 |
Yun Li1,2, Jianxin Fu1,3, Yun Ling1,4, Tadayuki Yago3, J Michael McDaniel3, Jianhua Song3, Xia Bai1,2, Yuji Kondo3, Yannan Qin3,5, Christopher Hoover3, Samuel McGee3, Bojing Shao3, Zhenghui Liu3, Roberto Sonon6, Parastoo Azadi6, Jamey D Marth7, Rodger P McEver3,8, Changgeng Ruan1,2, Lijun Xia9,2,3,8.
Abstract
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.Entities:
Keywords: Kupffer cell; O-glycan; clearance; platelet
Mesh：
Substances：
Year: 2017 PMID： 28716912 PMCID： PMC5547648 DOI： 10.1073/pnas.1707662114
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205