RECEPTORS INVOLVED IN CARBOHYDRATE-BINDING MODULATE INTESTINAL EPITHELIAL-NEUTROPHIL INTERACTIONS
RECEPTORS INVOLVED IN CARBOHYDRATE-BINDING MODULATE INTESTINAL EPITHELIAL-NEUTROPHIL INTERACTIONS
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DOI：
10.1074/jbc.270.18.10531
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发表时间：
1995-05-05
影响因子：
4.8
通讯作者：
MADARA, JL
中科院分区：
文献类型：
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作者：
COLGAN, SP;PARKOS, CA;MADARA, JL
中性粒细胞（多形核中性粒细胞）跨上皮屏障迁移是许多疾病的常见形态特征。先前的研究表明，PMN-上皮相互作用依赖于 PMN β(2)-整合素 CD11b/18；然而，我们对表面碳水化合物和中性粒细胞上皮相互作用一无所知。在这里，我们使用中性粒细胞和肠上皮细胞系 T84 的培养单层研究碳水化合物对中性粒细胞-上皮相互作用的作用。添加碳水化合物 6-磷酸甘露糖 (Man-6-P) 和 6-磷酸葡萄糖 (Glu-6-P)，但不添加 1-磷酸果糖 (Fru-1-P)，可抑制轮回大于或等于 70%。同样，更复杂的碳水化合物，如岩藻多糖和富含 Man-B-6 的多糖 PPME 选择性抑制 PMN 跨上皮迁移。发现这些碳水化合物在顶端到基底外侧方向以及基底外侧到顶端方向上具有抑制作用，表明缺乏极性。然而，这组相关碳水化合物不能有效调节 PMN 与上皮单层的短期粘附，表明碳水化合物配体可能调节轮回级联中的不同步骤。最后，添加对选择素（CD62E、CD62L 和 CD62P）具有特异性的功能性抑制性单克隆抗体显示对 PMN 迁移没有可观察到的影响。这些研究表明细胞表面碳水化合物可能在肠道炎症过程中发挥作用。
Neutrophil (polymorphonuclear neutrophil) migration across epithelial barriers is a common morphologic feature of many diseases. Previous studies show that PMN-epithelial interactions are dependent on the PMN beta(2)-integrin CD11b/18; however, nothing is known about surface carbohydrates and PMN epithelial interactions. Here we investigate the role of carbohydrates on PMN-epitehlial interactions using PMN and cultured monolayers of the intestinal epithelial cell line T84. Addition of the carbohydrates mannose 6-phosphate (Man-6-P) and glucose 6-phosphate (Glu-6-P), but not fructose 1-phosphate (Fru-1-P) inhibited transmigration by greater than or equal to 70%. Likewise, more complex carbohydrates, such as fucoidin and the Man-B-6-rich polysaccharide PPME selectively inhibited PMN transepithelial migration. These carbohydrates were found to be inhibitory in the apical-to-basolateral direction as well as the basolateral-to-apical direction, indicating a lack of polarity. This panel of related carbohydrates, however, was not effective in modulating short-term adhesion of PMN to epithelial monolayers, indicating that carbohydrate ligands may modulate different steps in the transmigration cascade. Finally, addition of functionally inhibitory monoclonal antibodies specific for the selectins (CD62E, CD62L, and CD62P) revealed no observable effect on PMN transmigration. These studies suggest that cell surface carbohydrates may play a role in inflammatory processes of the intestine.