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

作者：Yun Li, Jianxin Fu, Yun Ling, Tadayuki Yago, J. Michael McDaniel, Jianhua Song, Xia Bai, Yuji Kondo, Yannan Qin, Christopher M. Hoover, Samuel McGee, Bojing Shao, Zhenghui Liu, R.N. Sonon, Parastoo Azadi, Jamey D. Marth, Rodger P. McEver, Changgeng Ruan, Lijun Xia · 发表于：Proceedings of the National Academy of Sciences · 年份：2017 · DOI：10.1073/pnas.1707662114 · 被引用次数：120 · 研究领域：Glycosylation and Glycoproteins Research、Proteoglycans and glycosaminoglycans research、Carbohydrate Chemistry and Synthesis

Significance Although many platelet glycoproteins, such as GPIbα and GPIIb/IIIa, are predominately modified by O-glycans, the biological importance of O-glycans in platelet homeostasis is unclear. Here, we report that platelets lacking O-glycans exhibit a reduced life-span and increased clearance in the liver due to defective sialylation. We found that Kupffer cells play a major role in clearing desialylated O-glycan–deficient platelets in cooperation with hepatocytes via the hepatic asialoglycoprotein receptor. These findings reveal how O-glycosylation regulates platelet homeostasis and clearance; they may also provide insights into the pathogenesis of disorders with thrombocytopenia such as sepsis and immune thrombocytopenia refractory to splenectomy.