Key tissue targets responsible for anthrax-toxin-induced lethality.
Key tissue targets responsible for anthrax-toxin-induced lethality.
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炭疽芽孢杆菌是炭疽病的病原体，在炭疽致死毒素(LT)和水肿性毒素(ET)两种外毒素的作用下具有致死性。这些毒素致死效应的关键组织靶标尚不清楚。在这里，我们产生了细胞型特异性炭疽毒素受体毛细血管形态发生蛋白-2(CMG2)缺失的小鼠和细胞型特异性CMG2表达的小鼠，并用毒素攻击它们。我们的结果表明，LT和ET诱导的致死性是通过对不同细胞类型的损伤而发生的，而LT诱导的死亡需要靶向心肌细胞和血管平滑肌细胞，而ET诱导的致死性主要是通过其对肝细胞的作用而发生的。令人惊讶的是，与之前的假设相反，这两种毒素对内皮细胞的靶向似乎都没有显著的致命性。我们的发现表明，炭疽杆菌已经进化到使用LT和ET通过协同破坏两个不同的生命系统来诱导宿主死亡。
Bacillus anthracis, the causative agent of anthrax disease, is lethal due to the actions of two exotoxins, anthrax lethal toxin (LT) and edema toxin (ET). The key tissue targets responsible for the lethal effects of these toxins are unknown. Here we generated cell-type specific anthrax toxin receptor capillary morphogenesis protein-2 (CMG2)-null mice and cell-type specific CMG2-expressing mice and challenged them with the toxins. Our results show that lethality induced by LT and ET occur through damage to distinct cell-types; while targeting cardiomyocytes and vascular smooth muscle cells is required for LT-induced mortality, ET-induced lethality occurs mainly through its action in hepatocytes. Surprisingly, and in contradiction to what has been previously postulated, targeting of endothelial cells by either toxin does not appear to contribute significantly to lethality. Our findings demonstrate that B. anthracis has evolved to use LT and ET to induce host lethality by coordinately damaging two distinct vital systems.
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DOI：
10.1038/labinvest.2010.5
发表时间：
2010-04
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Hu, Haijing;Sa, Qila;Zhou, Daoguo
通讯作者：
Zhou, Daoguo
DOI：
10.1073/pnas.79.10.3162
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEPPLA, SH
通讯作者：
LEPPLA, SH
影响因子：
2.5
作者：
Alva, JA;Zovein, AC;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
30.3
作者：
Liu S;Miller-Randolph S;Crown D;Moayeri M;Sastalla I;Okugawa S;Leppla SH
通讯作者：
Leppla SH