Selective Activation of Human Intestinal Mast Cells by Escherichia coli Hemolysin1
Selective Activation of Human Intestinal Mast Cells by Escherichia coli Hemolysin1
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大肠杆菌溶血素1选择性激活人肠肥大细胞
DOI：
10.4049/jimmunol.181.2.1438
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
S. Bischoff
中科院分区：
文献类型：
--
作者：
S. Krämer;G. Sellge;A. Lorentz;Dagmar Krueger;M. Schemann;K. Feilhauer;F. Gunzer;S. Bischoff
肥大细胞（MC）被认为在细菌宿主防御中起重要作用。在这项研究中，我们研究了相互作用的人MCs，从肠道中分离和纯化到同质，与不同的大肠杆菌和志贺菌福氏菌株。结果表明，产α-溶血素（Hly）的E.大肠杆菌菌株诱导肠道MC释放组胺、白三烯和促炎细胞因子。相比之下，MC几乎对S无反应。flexneri和几株Hly阴性E.大肠杆菌菌株，包括Hly+菌株的同基因Hly缺陷突变体。Hly+ E.而不是Hly-E。coli引起细胞内Ca ~（2+）水平升高。用环孢菌素A阻断细胞外Ca ~（2+）和钙调蛋白/钙调神经磷酸酶途径可抑制对Hly+ E的反应。杆菌此外，MAPKs p38和ERK的抑制减少了Hly+ E对MC的激活。杆菌此外，我们还利用离体系统，直接记录了Hly+ E感染后，位于固有层中的MC释放组胺的情况。杆菌我们的数据表明，人肠道肥大细胞与选定的革兰氏阴性菌相互作用，建立E。coli Hly作为调节MC效应子功能的因子，进一步论证了人MC在先天免疫中的作用。
Mast cells (MCs) are recognized to play an important role in bacterial host defense in the murine system. In this study, we studied the interaction of human MCs, isolated from the intestine and purified to homogeneity, with different Escherichia coli and Shigella flexneri strains. We show that α-hemolysin (Hly)-producing E. coli strains induce the release of histamine, leukotrienes, and proinflammatory cytokines in intestinal MCs. In contrast, MCs were virtually unresponsive to S. flexneri and several Hly-negative E. coli strains, including the isogenic Hly-deficient mutants of Hly+ strains. Hly+ E. coli but not Hly− E. coli caused an increase in intracellular Ca2+ levels. Blocking of extracellular Ca2+ and of the calmodulin/calcineurin pathway by cyclosporin A inhibited the response to Hly+ E. coli. Furthermore, inhibition of MAPKs p38 and ERK reduces activation of MCs by Hly+ E. coli. In addition, using an ex vivo system, we directly record the histamine release by MCs located in the lamina propria after infection with Hly+ E. coli. Our data indicate that human intestinal mast cells interact with selected Gram-negative bacteria, establish E. coli Hly as a factor regulating MC effector functions, and argue further for a role of human MCs in innate immunity.
影响因子：
14.2
作者：
Kulka, M;Alexopoulou, L;Metcalfe, DD
通讯作者：
Metcalfe, DD
影响因子：
29.4
作者：
Barbara, G;Stanghellini, V;Corinalidesi, R
通讯作者：
Corinalidesi, R