Differential effects of Clostridium difficile toxins A and B on rabbit ileum.
Differential effects of Clostridium difficile toxins A and B on rabbit ileum.
复制标题
艰难梭菌毒素 A 和 B 对兔回肠的不同影响。
DOI：
10.1016/0016-5085(87)91014-6
复制
发表时间：
1987
期刊：
影响因子：
29.4
通讯作者：
LaMont,JT
中科院分区：
文献类型：
--
作者：
Triadafilopoulos,G;Pothoulakis,C;O'Brien,MJ;LaMont,JT
艰难梭菌小肠结肠炎的发病机制似乎涉及肠道定植，随后释放毒素A（一种肠毒素）和毒素B（一种细胞毒素）。本研究的目的是确定纯化的毒素 A 和 B 对灌注兔回肠环的肠道分泌、上皮通透性和形态的影响。通过[3H]甘露醇的血液到腔的清除率来评估毒素暴露后的肠通透性。与等浓度的毒素 B 或缓冲液对照相比，5–100 μg/10 cm 回肠环剂量的毒素 A 导致 [3H]甘露醇渗透性增加三至五倍（p < 0.001）。此外，与毒素 B 或对照环相比，来自毒素 A 暴露环的灌注液含有显着更多的中性粒细胞 (p < 0.001)。毒素A引起严重的上皮细胞坏死，伴有绒毛破坏和多形核浸润。受到低剂量毒素作用的粘膜的电子显微镜显示，内质网广泛非特异性扩张和线粒体肿胀。与毒素 A 在回肠环中的这些作用相反，短期器官培养中回肠外植体的体外实验表明，毒素 A 对上皮细胞通透性、蛋白质合成、碱性磷酸酶的释放或形态没有影响。我们的结果表明，纯化的毒素 A 而不是毒素 B 会导致兔回肠袢严重炎症性肠炎，但在体外对兔回肠没有明显影响。我们推测毒素 A 可能对 C 中的肠道损伤有显着影响。艰难梭菌相关性结肠炎和腹泻。
The pathogenesis ofClostridium difficileenterocolitis appears to involve colonization of the bowel followed by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. The purpose of this study was to determine the effect of purified toxins A and B on intestinal secretion, epithelial permeability, and morphology in perfused rabbit ileal loops. Intestinal permeability after toxin exposure was assessed by blood-to-lumen clearance of [3H]mannitol. Toxin A at doses of 5–100 μg/10 cm ileal loop caused a threefold to fivefold increase in [3H]mannitol permeability (p < 0.001) vs. equal concentrations of toxin B or buffer control. In addition, perfusate from toxin A-exposed loops contained significantly more neutrophils (p < 0.001) than toxin B or control loops. Toxin A caused severe epithelial cell necrosis with destruction of villi and polymorphonuclear infiltration. Electron microscopy of mucosa subjected to a low dose of toxin revealed widespread nonspecific dilatation of endoplasmic reticulum and mitochondrial swelling. In contrast to these effects of toxin A in ileal loops, in vitro experiments with ileal explants in short-term organ culture revealed that toxin A had no effect on epithelial cell permeability, protein synthesis, release of alkaline phosphatase, or morphology. Our results show that purified toxin A but not toxin B causes severe inflammatory enteritis in rabbit ileal loops, but has no discernable effect on rabbit ileum in vitro. We speculate that toxin A may contribute significantly to intestinal damage inC. difficile-associated colitis and diarrhea.