Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Aug 1;114(31):8360-8365. doi: 10.1073/pnas.1707662114. Epub 2017 Jul 17.

Sialylation on O-glycans protects platelets from clearance by liver Kupffer cells.

Author information

1
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
2
Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215006, China.
3
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104.
4
The First People's Hospital of Changzhou, Changzhou, Jiangsu 213000, China.
5
Department of Cell Biology and Genetics, School of Basic Medical Science, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
6
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602.
7
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, CA 93106.
8
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
9
Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; lijun-xia@omrf.org.

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.

KEYWORDS:

Kupffer cell; O-glycan; clearance; platelet

PMID:
28716912
PMCID:
PMC5547648
DOI:
10.1073/pnas.1707662114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center