N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules
N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules
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DOI：
10.1038/ni1259
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发表时间：
2005-11-01
影响因子：
30.5
通讯作者：
Fukuda, M
中科院分区：
文献类型：
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作者：
Kawashima, H;Petryniak, B;Fukuda, M
淋巴细胞归巢是由淋巴细胞上的 L-选择素与仅限于淋巴结高内皮小静脉的硫酸化碳水化合物之间的特异性相互作用介导的。在这里，我们生成了缺乏 N-乙酰氨基葡萄糖-6-O-磺基转移酶 1 (GlcNAc6ST-1) 和 GlcNAc6ST-2 的小鼠，发现突变小鼠的淋巴细胞归巢到外周淋巴结的次数比野生型小鼠少约 75%。因此，这些小鼠的接触超敏反应比野生型小鼠低。碳水化合物结构分析表明，L-选择素的主要配体6-磺基唾液酸Lewis X在这些突变小鼠的高内皮微静脉中几乎完全不存在，而未硫酸化的唾液酸Lewis X的量要大得多。这些结果证明了 GlcNAc6ST-1 和 GlcNAc6ST-2 在高内皮微静脉中 L-选择素配体生物合成中的基本功能及其在免疫监视中的重要性。
Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O- sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.