Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa
Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa
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DOI：
10.4049/jimmunol.164.6.3368
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发表时间：
2000-03-15
影响因子：
4.4
通讯作者：
Reinecker, HC
中科院分区：
文献类型：
--
作者：
Muehlhoefer, A;Saubermann, LJ;Reinecker, HC
Fractalkine 是一种独特的趋化因子，结合了趋化剂和粘附分子的特性，已在肠道中观察到 Fractalkine mRNA 的表达。然而，fratalkine 在健康肠道和炎症粘膜反应期间的作用尚不清楚，进行了研究以确定 fractalkine 和 fractalkine 受体 CX(3)CR1 在人小肠粘膜中的表达和功能，Wt？确定肠上皮细胞是 fractalkine 的新来源。肠上皮细胞系T-84中fratalkine mRNA和蛋白的基础表达受到炎症介质a-lp的控制。在用 IL-IP 刺激后，Fractalkine 从肠上皮细胞表面脱落。 Fractalkine 与 Caveolin-1 一起定位于 T-84 细胞中去污剂不溶性富含糖脂的膜微域中。 fractalkine 的细胞分布在 T-84 细胞极化过程中受到调节。分离的人肠上皮内淋巴细胞亚群表达 fractalkine 受体 CX(3)CR1，并在用 IL-2 激活后沿着 fractalkine 梯度特异性迁移，免疫组织化学证明正常小肠和活动性克罗恩病粘膜的肠上皮细胞和内皮细胞中存在 fractalkine 表达，此外，活动性克罗恩病期间肠道中 fractalkine mRNA 表达显着上调，本研究表明fractalkine-CX(3)CR1 介导的机制可能指导健康和患病人类小肠粘膜内的淋巴细胞趋化和粘附。
Fractalkine is a unique chemokine that combines properties of both chemoattractants and adhesion molecules, Fractalkine mRNA expression has been observed in the intestine. However, the role of fractalkine in the healthy intestine and during inflammatory mucosal responses is not known, Studies were undertaken to determine the expression and function of fractalkine and the fractalkine receptor CX(3)CR1 in the human small intestinal mucosa, Wt? identified intestinal epithelial cells as a novel source of fractalkine. The basal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator a-lp. Fractalkine was shed from intestinal epithelial cell surface upon stimulation with IL-IP. Fractalkine localized with caveolin-1 in detergent-insoluble glycolipid-enriched membrane microdomains in T-84 cells. Cellular distribution of fractalkine was regulated during polarization of T-84 cells. A subpopulation of isolated human intestinal intra-epithelial lymphocytes expressed the fractalkine receptor CX(3)CR1 and migrated specifically along fractalkine gradients after activation with IL-2, Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cells in normal small intestine and in active Crohn's disease mucosa, Furthermore, fractalkine mRNA expression was significantly up-regulated in the intestine during active Crohn's disease, This study demonstrates that fractalkine-CX(3)CR1-mediated mechanism may direct lymphocyte chemoattraction and adhesion within the healthy and diseased human small intestinal mucosa.