A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules
A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules
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DOI：
10.1038/ni1258
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发表时间：
2005-11-01
影响因子：
30.5
通讯作者：
Rosen, SD
中科院分区：
文献类型：
--
作者：
Uchimura, K;Gauguet, JM;Rosen, SD
淋巴细胞上的L-选择素与高内皮微静脉上的硫酸配体相互作用导致卷曲，这是淋巴细胞重新募集到外周淋巴结中的关键。外周结节地址蛋白代表一类被功能阻断单抗MECA-79识别的L-选择素配体。它的表位与唾液酸基6-磺基Lewis X重叠，后者是L-选择素识别决定簇。在缺乏两种N-乙酰氨基葡萄糖-6-O-磺基转移酶(GlcNAc6ST-1和GlcNAc6ST-2)的小鼠中，高内皮微静脉中的外周结节地址和唾液酸基6-磺基Lewis X均被清除，淋巴细胞归巢到外周淋巴结的数量显著减少，沿高内皮微静脉的黏附减少。我们的研究结果为磺基转移酶在L-选择素配体合成中的作用奠定了基础，可能对炎症性疾病的治疗有一定的指导意义。
The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules leads to rolling and is critical for recruitment of lymphocytes into peripheral lymph nodes. Peripheral node addressin represents a class of L-selectin ligands recognized by the function-blocking monoclonal antibody MECA-79. Its epitope overlaps with sialyl 6-sulfo Lewis X, an L-selectin recognition determinant. Here, mice lacking two N-acetylglucosamine-6-O-sulfotransferases (GlcNAc6ST-1 and GlcNAc6ST-2) demonstrated elimination of both peripheral node addressin and sialyl 6-sulfo Lewis X in high endothelial venules, considerably reduced lymphocyte homing to peripheral lymph nodes and reduced sticking of lymphocytes along high endothelial venules. Our results establish an essential function for the sulfotransferases in L-selectin ligand synthesis and may have relevance for therapy of inflammatory diseases.