Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation
Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation
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DOI：
10.1016/s1074-7613(00)80653-6
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发表时间：
1998-12-01
期刊：
影响因子：
32.4
通讯作者：
Marth, JD
中科院分区：
文献类型：
--
作者：
Ellies, LG;Tsuboi, S;Marth, JD
哺乳动物丝氨酸/苏氨酸连接的寡糖(O-多糖)通常由高尔基体核心2-β-1，6-N-乙酰氨基葡萄糖基转移酶(C2 GlcNAcT)合成。核心O-葡聚糖被认为对粘蛋白的产生和选择素配体的生物合成是必不可少的。我们报告，缺乏C2 GlcNAcT的小鼠表现出中性粒细胞增多和部分选择素配体缺乏的限制性表型。核心2寡糖的丢失减少了中性粒细胞在含有E-、L-和P-选择素的底物上的滚动，并减少了中性粒细胞重新聚集到炎症部位。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的归巢。这些研究表明，核心2寡糖的生物合成分离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。
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.