Farid Ayman Samir, Jimi Fumiko, Inagaki-Ohara Kyoko, Horii Yoichiro
Veterinary Teaching Hospital and Parasitology, Faculty of Agriculture, University of Miyazaki, Gakuen-Kibanadai, Miyazaki, Japan.
Shock. 2008 Jun;29(6):709-16. doi: 10.1097/shk.0b013e31815c3f36.
It is known that hypersensitivity reactions in the gastrointestinal tract, which are primarily mediated by mast cells, are associated with a secretory response of the epithelium and often increased permeability to macromolecules. Studies to date have not examined the effects of hyperpermeability on the absorption of toxic substances normally present in the intestinal lumen such as bacterial LPS. In the present study, we observed that Strongyloides venezuelensis infection in mice decreases the mRNA expression of intestinal epithelial cell junctional molecules (occludin and zonula occludens 1) and increases portal endotoxin levels 4 h after intragastric administration of LPS (20 mg/kg body weight). Furthermore, an increase in the flux of immunoglobulin G into the intestinal lumen was observed 10 days postinfection (PI). An increased rate of LPS absorption was also seen in mice infected with Nippostrongylus brasiliensis on day 14 PI and rats concurrently infected with S. venezuelensis and N. brasiliensis on day 20 PI. On the other hand, infection with Eimeria vermiformis and Eimeria pragensis was not observed to enhance LPS absorption 4 h after intragastric administration of LPS (20 mg/kg body weight), although E. vermiformis infection did inhibit the epithelial cell mRNA expression of zonula occludens 1, but not occludin, on day 9 PI, resulting in a reduced immunoglobulin G flux than that produced by S. venezuelensis infection. Our results suggest that mastocytosis accompanying intestinal nematode infection increases the intestinal absorption of LPS into the portal circulation by suppressing the expression of tight junction molecules.
已知胃肠道中的超敏反应主要由肥大细胞介导,与上皮细胞的分泌反应相关,且通常对大分子的通透性增加。迄今为止的研究尚未考察通透性增加对肠道内正常存在的有毒物质(如细菌脂多糖)吸收的影响。在本研究中,我们观察到,给小鼠胃内注射脂多糖(20毫克/千克体重)4小时后,委内瑞拉类圆线虫感染会降低肠道上皮细胞连接分子(闭合蛋白和闭合小带蛋白1)的mRNA表达,并增加门静脉内毒素水平。此外,感染后10天观察到免疫球蛋白G进入肠腔的通量增加。在感染巴西日圆线虫的小鼠感染后第14天,以及同时感染委内瑞拉类圆线虫和巴西日圆线虫的大鼠感染后第20天,也观察到脂多糖吸收速率增加。另一方面,给小鼠胃内注射脂多糖(20毫克/千克体重)4小时后,未观察到感染蠕形艾美耳球虫和普拉热艾美耳球虫会增强脂多糖吸收,尽管在感染后第9天,蠕形艾美耳球虫感染确实抑制了闭合小带蛋白1的上皮细胞mRNA表达,但未抑制闭合蛋白的表达,导致免疫球蛋白G通量低于委内瑞拉类圆线虫感染所产生的通量。我们的结果表明,肠道线虫感染伴随的肥大细胞增多症通过抑制紧密连接分子的表达增加了脂多糖向门静脉循环的肠道吸收。