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

被引:259
作者
Ellies, LG
Tsuboi, S
Petryniak, B
Lowe, JB
Fukuda, M
Marth, JD [1 ]
机构
[1] Univ Calif San Diego, Howard Hughes Med Inst, Div Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Burnham Inst, La Jolla, CA 92037 USA
[3] Univ Michigan, Sch Med, Dept Pathol, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA
关键词
D O I
10.1016/S1074-7613(00)80653-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:881 / 890
页数:10
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