Action of shiga toxin type-2 and subtilase cytotoxin on human microvascular endothelial cells.
Action of shiga toxin type-2 and subtilase cytotoxin on human microvascular endothelial cells.
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DOI：
10.1371/journal.pone.0070431
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ibarra C
中科院分区：
文献类型：
--
作者：
Amaral MM;Sacerdoti F;Jancic C;Repetto HA;Paton AW;Paton JC;Ibarra C
溶血性尿毒综合征（HUS）是由产滋贺毒素（Stx）大肠杆菌（STEC）感染引起的并发症。在阿根廷，溶血尿毒综合征是一种地方病，可导致5岁以下儿童的急性和慢性肾衰竭。由于存在非常Stx敏感的细胞，如微血管内皮细胞，人类肾脏是受影响最严重的器官。最近，枯草杆菌酶细胞毒素（SubAB）被认为是一种新的毒素，可能有助于HUS的发病机制，但它对人肾小球内皮细胞（HGEC）的作用尚未被描述。在这项研究中，我们比较了SubAB与Stx 2对从人小儿肾皮质碎片中分离的HGEC原代培养物的影响。由于HGEC表达血管性血友病因子（VWF）和血小板/内皮细胞粘附分子1（PECAM-1），因此HGEC被表征为内皮细胞。HGEC还表达Stx 2的globotriaosylceramide（Gb 3）受体。Stx 2和SubAB均诱导HGEC肿胀和脱离，并以时间依赖性方式降低细胞活力。HGEC与C-9 −（一种Gb 3合成的竞争性抑制剂）预孵育可保护HGEC免受Stx 2的影响，但不受SubAB细胞毒性作用的影响。Stx 2以时间依赖性方式增加细胞凋亡，而SubAB在4和6 h增加细胞凋亡，但在24 h减少。SubAB诱导的细胞凋亡在4 h和6 h高于Stx 2，而在24 h低于Stx 2。此外，在评价的所有时间点，Stx 2引起的坏死显著高于SubAB诱导的坏死。我们的数据首次提供了SubAB如何与HUS发病机制的内皮损伤特征的发展合作的证据。
The hemolytic uremic syndrome (HUS) associated with diarrhea is a complication of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection. In Argentina, HUS is endemic and responsible for acute and chronic renal failure in children younger than 5 years old. The human kidney is the most affected organ due to the presence of very Stx-sensitive cells, such as microvascular endothelial cells. Recently, Subtilase cytotoxin (SubAB) was proposed as a new toxin that may contribute to HUS pathogenesis, although its action on human glomerular endothelial cells (HGEC) has not been described yet. In this study, we compared the effects of SubAB with those caused by Stx2 on primary cultures of HGEC isolated from fragments of human pediatric renal cortex. HGEC were characterized as endothelial since they expressed von Willebrand factor (VWF) and platelet/endothelial cell adhesion molecule 1 (PECAM-1). HGEC also expressed the globotriaosylceramide (Gb3) receptor for Stx2. Both, Stx2 and SubAB induced swelling and detachment of HGEC and the consequent decrease in cell viability in a time-dependent manner. Preincubation of HGEC with C-9 −a competitive inhibitor of Gb3 synthesis-protected HGEC from Stx2 but not from SubAB cytotoxic effects. Stx2 increased apoptosis in a time-dependent manner while SubAB increased apoptosis at 4 and 6 h but decreased at 24 h. The apoptosis induced by SubAB relative to Stx2 was higher at 4 and 6 h, but lower at 24 h. Furthermore, necrosis caused by Stx2 was significantly higher than that induced by SubAB at all the time points evaluated. Our data provide evidence for the first time how SubAB could cooperate with the development of endothelial damage characteristic of HUS pathogenesis.
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影响因子：
3.1
作者：
Matsuura, Gen;Morinaga, Naoko;Noda, Masatoshi
通讯作者：
Noda, Masatoshi
影响因子：
20.3
作者：
Matussek, A;Lauber, J;Gunzer, F
通讯作者：
Gunzer, F
影响因子：
64.8
作者：
Byres, Emma;Paton, Adrienne W.;Paton, James C.;Lofling, Jonas C.;Smith, David F.;Wilce, Matthew C. J.;Talbot, Ursula M.;Chong, Damien C.;Yu, Hai;Huang, Shengshu;Chen, Xi;Varki, Nissi M.;Varki, Ajit;Rossjohn, Jamie;Beddoe, Travis
通讯作者：
Beddoe, Travis
影响因子：
5.8
作者：
Creydt, VP;Silberstein, C;Ibarra, C
通讯作者：
Ibarra, C
影响因子：
--
作者：
Obrig, Tom G.;Karpman, Diana
通讯作者：
Karpman, Diana