Percy W H, Burakoff R, Rose K, Desai H P, Pothoulakis C, Eglow R
Department of Physiology and Pharmacology, School of Medicine, University of South Dakota, Vermillion, South Dakota 57069, USA.
Am J Physiol. 1998 Sep;275(3):G402-9. doi: 10.1152/ajpgi.1998.275.3.G402.
In the rabbit ileum Clostridium difficile toxin A causes inflammation and mucosal damage via a specific glycoprotein receptor that contains alpha-D-galactose. In rabbit colon toxin A also causes inflammation, and this is associated with increased myoelectric activity and eicosanoid production. The present in vitro study was undertaken to determine if a toxin A receptor on one or more layers of colonic smooth muscle could mediate the motor effects of this agent. Toxin A (20-100 microg/ml) was without effect on longitudinal and circular muscle but had two different effects on the muscularis mucosae. Initial exposure to the toxin caused increased numbers of spontaneous contractions and a small, atropine-, tetrodotoxin-, and indomethacin-resistant increase in resting tone. More importantly, however, 30-min exposure to toxin A resulted in attenuated muscularis mucosae responses to acetylcholine and K+. Both the small excitatory and the larger inhibitory effects of toxin A were abolished by pretreatment with the lectin BS-1, which binds to toxin A receptors, but not by the nonreceptor-binding lectin DBA. These data strongly suggest that toxin A causes significant motor effects on the distal colonic muscularis mucosae via a receptor-mediated mechanism. These mechanical data were supported by the presence of histologically demonstrable toxin A and BS-1 binding sites on the muscularis mucosae but not on either the longitudinal or circular muscle layers, both of which were unresponsive to the toxin. By depressing muscularis mucosae function and, ultimately, mucosal movement as a result of toxin A production, C. difficile may promote its own proliferation, thus further contributing to the development of antibiotic-associated colitis.
在兔回肠中，艰难梭菌毒素A通过一种含有α-D-半乳糖的特异性糖蛋白受体引起炎症和黏膜损伤。在兔结肠中，毒素A也会引发炎症，这与肌电活动增加和类花生酸生成有关。本体外研究旨在确定结肠平滑肌一层或多层上的毒素A受体是否能介导该因子的运动效应。毒素A（20 - 100微克/毫升）对纵行肌和环行肌无作用，但对黏膜肌层有两种不同影响。最初接触毒素会导致自发收缩次数增加，以及静息张力出现小幅度、对阿托品、河豚毒素和吲哚美辛不敏感的升高。然而，更重要的是，接触毒素A 30分钟会导致黏膜肌层对乙酰胆碱和钾离子的反应减弱。毒素A的小兴奋性作用和大抑制性作用都可通过与毒素A受体结合的凝集素BS - 1预处理消除，但非受体结合凝集素DBA则不能。这些数据有力地表明，毒素A通过受体介导机制对远端结肠黏膜肌层产生显著的运动效应。组织学上可证明黏膜肌层存在毒素A和BS - 1结合位点，而纵行肌层和环行肌层均无，且这两层对毒素无反应，这些力学数据支持了上述观点。通过抑制黏膜肌层功能，并最终因毒素A的产生而抑制黏膜运动，艰难梭菌可能促进自身增殖，从而进一步导致抗生素相关性结肠炎的发展。
