Increased intestinal endotoxin absorption during enteric nematode but not protozoal infections through a mast cell-mediated mechanism
Increased intestinal endotoxin absorption during enteric nematode but not protozoal infections through a mast cell-mediated mechanism
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DOI：
10.1097/shk.0b013e31815c3f36
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发表时间：
2008-06-01
期刊：
影响因子：
3.1
通讯作者：
Horii, Yoichiro
中科院分区：
文献类型：
--
作者：
Farid, Ayman Samir;Jimi, Fumiko;Horii, Yoichiro
已知胃肠道中主要由肥大细胞介导的超敏反应与上皮的分泌反应相关，并且通常增加对大分子的渗透性。迄今为止的研究尚未检查过通透性过高对肠腔中通常存在的毒性物质（如细菌LPS）吸收的影响。在本研究中，我们观察到，在小鼠体内的圆线虫感染降低肠上皮细胞连接分子（闭合蛋白和闭锁小带1）的mRNA表达，并增加门静脉内毒素水平4小时后，灌胃LPS（20 mg/kg体重）。此外，增加流入肠腔的免疫球蛋白G的流量，观察感染后10天（PI）。在感染巴西日本圆线虫的小鼠和同时感染S. venezuelensis和N.在第20天PI.另一方面，在灌胃给予LPS（20 mg/kg体重）后4 h，未观察到蠕虫状艾美耳球虫和草地艾美耳球虫感染增强LPS吸收，尽管蠕虫状艾美耳球虫感染在PI第9天确实抑制了上皮细胞闭锁小带1的mRNA表达，但不抑制闭锁蛋白的mRNA表达，导致免疫球蛋白G通量比S.委内瑞拉感染我们的研究结果表明，肥大细胞增多症伴随肠道线虫感染增加了肠道吸收的LPS进入门静脉循环抑制紧密连接分子的表达。
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.