Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery
Clostridium perfringens epsilon-toxin increases permeability of single perfused microvessels of rat mesentery
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DOI：
10.1128/iai.73.8.4879-4887.2005
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发表时间：
2005-08-01
影响因子：
3.1
通讯作者：
Curry, FE
中科院分区：
文献类型：
--
作者：
Adamson, RH;Ly, JC;Curry, FE
ε-毒素是D型产气荚膜梭菌的主要毒力因子，可导致家畜死亡，特别是绵羊和山羊，其中它可诱导通常致命的肠毒血症。它被认为破坏肠屏障，然后进入肠道脉管系统，从那里全身携带，引起广泛的血管内皮损伤和水肿。在这里，我们使用单一灌注的小静脉微血管在大鼠肠系膜，这使得直接观察的通透性特性的血管壁在暴露于毒素。我们测定了微血管的水力传导率（LP）作为对ε毒素的反应的量度。我们发现微血管对毒素高度敏感。在10 μ g ml（-1）时，LP在10分钟内不可逆地增加到对照值的15倍以上。在0.3 μ g ml（-1）时，在长达90分钟内未观察到L-p增加。毒素诱导的L-p增加与暴露于毒素的微血管超微结构变化一致。这些微血管在内皮细胞之间或通过内皮细胞存在间隙，灌注液可直接进入基底膜。许多内皮细胞出现坏死，高度衰减，并具有致密的胞浆。我们发现，ε毒素，在时间和剂量依赖性的方式，迅速和不可逆地损害微静脉内皮细胞的屏障功能。结果证实了ε毒素与血管内皮细胞相互作用，通过直接损伤内皮细胞增加血管壁通透性的假设。
Epsilon-toxin, the primary virulence factor of Clostridium perfringens type D, causes mortality in livestock, particularly sheep and goats, in which it induces an often-fatal enterotoxemia. It is believed to compromise the intestinal barrier and then enter the gut vasculature, from which it is carried systemically, causing widespread vascular endotheliall damage and edema. Here we used single perfused venular microvessels in rat mesentery, which enabled direct observation of permeability properties of the in situ vascular wall during exposure to toxin. We determined the hydraulic conductivity (LP) of microvessels as a measure of the response to epsilon-toxin. We found that microvessels were highly sensitive to toxin. At 10 mu g ml(-1) the LP increased irreversibly to more than 15 times the control value by 10 min. At 0.3 mu g ml(-1) no increase in L-p was observed for up to 90 min. The toxin-induced increase in L, was consistent with changes in ultrastructure of microvessels exposed to the toxin. Those microvessels exhibited gaps either between or through endotheliall cells where perfusate had direct access to the basement membrane. Many endothelial cells appeared necrotic, highly attenuated, and with dense cytoplasm. We showed that epsilon-toxin, in a time- and dose-dependent manner, rapidly and irreversibly compromised the barrier function of venular microvessel endothelium. The results conformed to the hypothesis that epsilon-toxin interacts with vascular endothelial cells and increases the vessel wall permeability by direct damage of the endothelium.