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双向FcRn依赖的IgG在极化人肠上皮细胞系中的转运

Bidirectional FcRn-dependent IgG transport in a polarized human intestinal epithelial cell line.

作者信息

Dickinson B L, Badizadegan K, Wu Z, Ahouse J C, Zhu X, Simister N E, Blumberg R S, Lencer W I

机构信息

The Combined Program in Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

出版信息

J Clin Invest. 1999 Oct;104(7):903-11. doi: 10.1172/JCI6968.

Abstract

The MHC class I-related Fc receptor, FcRn, mediates the intestinal absorption of maternal IgG in neonatal rodents and the transplacental transport of maternal IgG in humans by receptor-mediated transcytosis. In mice and rats, expression of FcRn in intestinal epithelial cells is limited to the suckling period. We have recently observed, however, clear expression of FcRn in the adult human intestine, suggesting a function for FcRn in intestinal IgG transport beyond neonatal life in humans. We tested this hypothesis using the polarized human intestinal T84 cell line as a model epithelium. Immunocytochemical data show that FcRn is present in T84 cells in a punctate apical pattern similar to that found in human small intestinal enterocytes. Solute flux studies show that FcRn transports IgG across T84 monolayers by receptor-mediated transcytosis. Transport is bidirectional, specific for FcRn, and dependent upon endosomal acidification. These data define a novel bidirectional mechanism of IgG transport across epithelial barriers that predicts an important effect of FcRn on IgG function in immune surveillance and host defense at mucosal surfaces.

摘要

与MHC I类相关的Fc受体FcRn,通过受体介导的转胞吞作用介导新生啮齿动物肠道对母体IgG的吸收以及人类母体IgG的胎盘转运。在小鼠和大鼠中,肠道上皮细胞中FcRn的表达仅限于哺乳期。然而,我们最近观察到,FcRn在成年人类肠道中有明显表达,这表明FcRn在人类新生儿期后的肠道IgG转运中具有功能。我们使用极化的人类肠道T84细胞系作为模型上皮来验证这一假设。免疫细胞化学数据显示,FcRn以点状顶端模式存在于T84细胞中,类似于在人类小肠肠细胞中发现的模式。溶质通量研究表明,FcRn通过受体介导的转胞吞作用将IgG转运穿过T84单层。转运是双向的,对FcRn具有特异性,并依赖于内体酸化。这些数据定义了一种IgG跨上皮屏障转运的新型双向机制,预测FcRn对黏膜表面免疫监视和宿主防御中IgG功能具有重要影响。

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