Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration
Endothelial damage induced by Shiga toxins delivered by neutrophils during transmigration
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DOI：
10.1189/jlb.0709475
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发表时间：
2010-07-01
影响因子：
5.5
通讯作者：
Caprioli, Alfredo
中科院分区：
文献类型：
--
作者：
Brigotti, Maurizio;Tazzari, Pier Luigi;Caprioli, Alfredo
由Stx诱导的内皮损伤代表了与人类STEC感染相关的HUS中的主要致病事件。由细菌在肠道中释放的Stx进入血液并靶向肾内皮。中性粒细胞作为毒素载体的作用一直是有争议的对象。在本文中，我们证实了结合的Stx 1的PMN，也显示其对满载的白细胞的脱粒作用，并支持的载体作用的PMN，通过使用两个腔室的transmigration装置，其中PMN，负载在体外与不同量的Stx 1，transmigration通过汇合的单层内皮细胞，模仿毒素诱导的肾内皮细胞损伤。Stx 1在PMN迁移过程中转移，损害蛋白质合成并触发内皮细胞中促炎细胞因子的产生。携带低毒素量的中性粒细胞，诱导释放高水平的细胞因子在活的内皮细胞，而细胞因子的产生被阻断在细胞的挑战与中性粒细胞满载Stx作为一个几乎完全损害的翻译和激活的凋亡程序的结果。与之前在动物模型中无法解释的观察结果一致，我们的实验结果表明，低剂量毒素引发的自放大循环可能导致HUS中肾损伤的促炎介质的产生。J. Leukoc. 88：201-210; 2010.
The endothelial damage induced by Stx represents the main pathogenic event in the HUS associated with STEC infections in humans. Stx, released in the gut by bacteria, enter the bloodstream and are targeted to renal endothelia. The role of PMN as a toxin carrier has been the object of controversy. In this paper, we confirm the binding of Stx1 to PMN, also showing its degranulating effects on full-loaded leukocytes, and support the carrier role of PMN by using a two- chamber transmigration device, in which PMN, loaded in vitro with different amounts of Stx1, transmigrated through confluent monolayers of endothelial cells, mimicking the toxin-induced renal endothelial injury. Stx1 was transferred during PMN transmigration, impairing protein synthesis and triggering production of proinflammatory cytokines in endothelial cells. PMN, carrying low toxin amounts, induced the release of high levels of cytokines in viable endothelial cells, whereas cytokine production was blocked in cells challenged with PMN fully loaded with Stx as a result of an almost total impairment of translation and of the activation of the apoptotic program. In agreement with previous unexplained observations in animal models, the results obtained with our experimental setting suggest that a self-amplifying circle triggered by low doses of toxin may lead to the production of proinflammatory mediators of renal damage in HUS. J. Leukoc. Biol. 88: 201-210; 2010.