Function of E-cadherin and mast cell proliferation in nematode infection

在呼吸道和肠道黏膜中分化的肥大细胞(粘膜型肥大细胞：MMC)在过敏性呼吸道炎症、线虫引起的炎症和蠕虫负担清除中发挥关键作用。我们发现在IL-3和IL-4的共同作用下培养的小鼠骨髓细胞和人肥大细胞系HMC-1表达E-钙粘素，在干细胞因子、IL-3、IL-9和转化生长因子-β1四种细胞因子联合培养的骨髓细胞中表达E-钙粘素和与E-钙粘素异嗜性结合的Ae 67整合素。本研究旨在阐明包括E-钙粘附素在内的细胞黏附分子在粘膜型肥大细胞中的表达和功能。RT-荧光定量聚合酶链式反应检测联合应用SCF、IL-3、IL-9和转化生长因子-β-1后，α-EB7整合素、上皮细胞黏附分子、ZO-1和纽蛋白表达上调。流式细胞仪检测显示，BMMC高水平表达ae67整合素和EP-CAM。EP-CAM是一种大小为39-42 kDa的钙非依赖性嗜同型细胞黏附分子，在大多数上皮组织中均有表达。ZO-1是紧密连接相关蛋白，与肌动蛋白细胞骨架结合。纽蛋白是粘着斑块中的一种膜-细胞骨架蛋白，参与E-钙粘蛋白与肌动蛋白细丝的连接。这些结果提示，粘膜型肥大细胞上表达的E-钙粘附素、αE-β7整合素、EP-CAM、ZO-1和vinculin可能在肥大细胞在肠粘膜内的迁移、选择性定位或滞留中起关键作用。

Mast cells that are differentiated in the respiratory and gut mucosa (mucosal-type mast cells : MMC) play a pivotal role in the development of allergic inflammation of the airways, nematode-induced inflammation, and worm burden clearance. We demonstrated that murine BMMC grown in the presence of IL-3 and IL-4 and the human mast cell line HMC-1 expressed E-cadherin, and BMMC cultured with a combination of four cytokines, SCF, IL-3, IL-9 and TGF-β1 expressed E-cadherin and aE67 integrin which binds to E-cadherin heterophilically. The present study aimed at elucidation of the expression and function of cell adhesion molecules included E-cadherin in mucosal type mast cells. The gene expression of BMMC cultured with a combination of SCF, IL-3, IL-9 and TGF-β1 by reserve transcription (RT)-realtime PCR showed that αEB7 integrin, Ep-CAM (Epithelial cell adhesion molecule), ZO-1 (zonula occludin) and Vinculin were upregulated. FACS analysis showed that BMMC expressed aE67 integrin and Ep-CAM at high levels. Ep-CAM is a calcium-independent homophilic cell adhesion molecule of 39-42 kDa which is expressed by the majority of epithelial tissues. ZO-1 was tight junction-associated proteins and joining to the actin cytoskeleton. Vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of E-cadherin to the actin filament. These results suggest that E-cadherin, αEβ7 integrin, Ep-CAM, ZO-1 and Vinculin expressed on mucosal-type mast cells might play a critical role in cell migration, selective localization, or retention of mast cells within gut mucosa.