Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils.
Salmonella typhimurium attachment to human intestinal epithelial monolayers: transcellular signalling to subepithelial neutrophils.
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DOI：
10.1083/jcb.123.4.895
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发表时间：
1993-11
影响因子：
7.8
通讯作者：
Madara, J L
中科院分区：
文献类型：
--
作者：
McCormick, B A;Colgan, S P;Delp-Archer, C;Miller, S I;Madara, J L
在由鼠伤寒沙门氏菌引起的人类肠道疾病中，嗜中性粒细胞（PMN）的跨上皮迁移迅速跟随细菌附着到上皮顶端膜。在这份报告中，我们在体外模拟这些相互作用，使用极化单层的人肠上皮细胞，T84，分离的人中性粒细胞，和S。鼠伤寒。我们表明，沙门氏菌附着T84细胞顶端膜并没有改变单层完整性评估的跨上皮电阻和离子转运的测量。然而，当人类中性粒细胞随后被放置在由沙门氏菌顶部定殖的单层的基底外侧表面上时，随后发生了生理定向的经上皮PMN迁移。与此相反，附着的非致病性大肠杆菌菌株的上皮细胞的顶膜在可比的密度未能刺激直接的中性粒细胞跨上皮迁移。使用N-甲酰肽受体拮抗剂N-t-BOC-1-甲硫氨酰-1-亮氨酰-1-苯丙氨酸（tBOC-MLP）表明，沙门氏菌诱导的PMN跨上皮迁移反应不是细菌诱导PMN定向迁移的经典途径。此外，中性粒细胞的迁移反应需要沙门氏菌粘附到上皮顶端膜和随后的相互蛋白质合成在细菌和上皮细胞。这种相互作用刺激的事件之一是上皮合成和极化释放的有效PMN趋化肽白细胞介素-8（IL-8）。然而，IL-8的中和，转移和诱导实验表明，这种细胞因子是不负责引起的中性粒细胞迁移。这些数据表明，存在一种新的跨细胞途径，其中上皮下中性粒细胞响应腔病原体在一个功能完整的上皮。基于肠粘膜已知的独特特征，我们推测IL-8可能与一种尚未鉴定的跨细胞趋化因子（TCF）协同作用，后者指导PMN迁移穿过肠上皮。
In human intestinal disease induced by Salmonella typhimurium, transepithelial migration of neutrophils (PMN) rapidly follows attachment of the bacteria to the epithelial apical membrane. In this report, we model those interactions in vitro, using polarized monolayers of the human intestinal epithelial cell, T84, isolated human PMN, and S. typhimurium. We show that Salmonella attachment to T84 cell apical membranes did not alter monolayer integrity as assessed by transepithelial resistance and measurements of ion transport. However, when human neutrophils were subsequently placed on the basolateral surface of monolayers apically colonized by Salmonella, physiologically directed transepithelial PMN migration ensued. In contrast, attachment of a non-pathogenic Escherichia coli strain to the apical membrane of epithelial cells at comparable densities failed to stimulate a directed PMN transepithelial migration. Use of the n-formyl-peptide receptor antagonist N-t-BOC-1-methionyl-1-leucyl-1- phenylalanine (tBOC-MLP) indicated that the Salmonella-induced PMN transepithelial migration response was not attributable to the classical pathway by which bacteria induce directed migration of PMN. Moreover, the PMN transmigration response required Salmonella adhesion to the epithelial apical membrane and subsequent reciprocal protein synthesis in both bacteria and epithelial cells. Among the events stimulated by this interaction was the epithelial synthesis and polarized release of the potent PMN chemotactic peptide interleukin-8 (IL-8). However, IL-8 neutralization, transfer, and induction experiments indicated that this cytokine was not responsible for the elicited PMN transmigration. These data indicate that a novel transcellular pathway exists in which subepithelial PMN respond to lumenal pathogens across a functionally intact epithelium. Based on the known unique characteristics of the intestinal mucosa, we speculate that IL-8 may act in concert with an as yet unidentified transcellular chemotactic factor(s) (TCF) which directs PMN migration across the intestinal epithelium.