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核心2寡糖生物合成区分了对白细胞归巢和炎症至关重要的选择素配体。

Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.

作者信息

Ellies L G, Tsuboi S, Petryniak B, Lowe J B, Fukuda M, Marth J D

机构信息

Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, University of California San Diego, La Jolla 92093, USA.

出版信息

Immunity. 1998 Dec;9(6):881-90. doi: 10.1016/s1074-7613(00)80653-6.

DOI:10.1016/s1074-7613(00)80653-6
PMID:9881978
Abstract

Mammalian serine/threonine-linked oligosaccharides (O-glycans) are commonly synthesized with the Golgi enzyme core 2 beta-1,6-N-acetylglucosaminyltransferase (C2 GlcNAcT). Core 2 O-glycans have been hypothesized to be essential for mucin production and selectin ligand biosynthesis. We report that mice lacking C2 GlcNAcT exhibit a restricted phenotype with neutrophilia and a partial deficiency of selectin ligands. Loss of core 2 oligosaccharides reduces neutrophil rolling on substrata bearing E-, L-, and P-selectins and neutrophil recruitment to sites of inflammation. However, the diminished presence of L-selectin ligands on lymph node high endothelial venules does not affect lymphocyte homing. These studies indicate that core 2 oligosaccharide biosynthesis segregates the physiologic roles of selectins and reveal a function for the C2 GlcNAcT in myeloid homeostasis and inflammation.

摘要

哺乳动物的丝氨酸/苏氨酸连接寡糖(O-聚糖)通常由高尔基体酶核心2β-1,6-N-乙酰葡糖胺基转移酶(C2 GlcNAcT)合成。核心2 O-聚糖被认为对粘蛋白产生和选择素配体生物合成至关重要。我们报告,缺乏C2 GlcNAcT的小鼠表现出中性粒细胞增多和选择素配体部分缺乏的受限表型。核心2寡糖的缺失减少了中性粒细胞在携带E-、L-和P-选择素的基质上滚动以及中性粒细胞向炎症部位的募集。然而,淋巴结高内皮微静脉上L-选择素配体的减少并不影响淋巴细胞归巢。这些研究表明,核心2寡糖生物合成区分了选择素的生理作用,并揭示了C2 GlcNAcT在髓系稳态和炎症中的功能。

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