Sulfated L-selectin ligands as a therapeutic target in chronic inflammation.
Sulfated L-selectin ligands as a therapeutic target in chronic inflammation.
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DOI：
10.1016/j.it.2006.10.007
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发表时间：
2006-12
影响因子：
16.8
通讯作者：
K. Uchimura;S. Rosen
中科院分区：
文献类型：
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作者：
K. Uchimura;S. Rosen
淋巴细胞向外周淋巴结的归巢是由淋巴细胞上的l -选择素和外周淋巴结寻址素（PNAd）之间的黏附相互作用启动的，PNAd是一组涎粘液蛋白，显示在淋巴结的高内皮小静脉（hev）上。单克隆抗体MECA-79通过识别n -乙酰氨基葡萄糖(GlcNAc)-6-硫酸寡糖与PNAd唾液蛋白发生反应，该寡糖与l -选择素识别决定因子唾液酰6-磺酰Lewis X重叠。两种hev表达的硫转移酶GlcNAc6ST-1和GlcNAc6ST-2对于淋巴结hev上MECA-79表位的表达和l -选择素配体活性至关重要。根据MECA-79染色的定义，PNAd也在慢性炎症的几个部位的活化血管上表达。最近的证据表明，相同的两种硫转移酶在这些位点形成功能性PNAd。绵羊哮喘模型实验表明，一种慢性炎症性疾病可以通过靶向PNAd得到改善。
The homing of lymphocytes to peripheral lymph nodes is initiated by an adhesive interaction between L-selectin on lymphocytes and peripheral node addressin (PNAd), a set of sialomucins displayed on high endothelial venules (HEVs) of lymph nodes. The monoclonal antibody MECA-79 reacts with the PNAd sialomucins by recognizing anN-acetylglucosamine (GlcNAc)-6-sulfated oligosaccharide, which overlaps with sialyl 6-sulfo Lewis X, the L-selectin recognition determinant. Two HEV-expressed sulfotransferases, GlcNAc6ST-1 and GlcNAc6ST-2, are essential for the expression of the MECA-79 epitope and L-selectin ligand activity on lymph-node HEVs. PNAd, as defined by MECA-79 staining, is also expressed on activated blood vessels at several sites of chronic inflammation. Recent evidence indicates that the same two sulfotransferases underlie the formation of functional PNAd at these sites. Experiments in a sheep model of asthma demonstrate that a chronic inflammatory disease can be ameliorated by targeting PNAd.