ENTEROTOXIN-INDUCED FLUID ACCUMULATION DURING EXPERIMENTAL SALMONELLOSIS AND CHOLERA - INVOLVEMENT OF PROSTAGLANDIN SYNTHESIS BY INTESTINAL-CELLS
ENTEROTOXIN-INDUCED FLUID ACCUMULATION DURING EXPERIMENTAL SALMONELLOSIS AND CHOLERA - INVOLVEMENT OF PROSTAGLANDIN SYNTHESIS BY INTESTINAL-CELLS
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DOI：
10.1016/0041-0101(85)90118-7
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发表时间：
1985-01-01
期刊：
影响因子：
2.8
通讯作者：
PETERSON, JW
中科院分区：
文献类型：
--
作者：
DUEBBERT, IE;PETERSON, JW
用鼠伤寒沙门氏菌或霍乱弧菌挑战兔肠袢导致粘膜cAMP和前列腺素浓度显著升高。这种效果可以再现在体外通过暴露于纯化的霍乱毒素或沙门氏菌的无细胞裂解物的正常兔或中国仓鼠卵巢细胞的分离的上皮细胞。吲哚美辛治疗的动物挑战沙门氏菌导致较少的液体积累，除了较低浓度的肠cAMP和alphandins，相比，在正常动物中的类似改变的循环。同样，用霍乱弧菌对吲哚美辛处理的兔进行肠袢攻击，其胰头素水平比未感染动物的组织高10倍。前列腺素水平在沙门氏菌感染的肠环同样升高，但只有2至3倍。将中国仓鼠卵巢细胞单层同时暴露于10 ng霍乱毒素或20 μ l沙门氏菌裂解物和范围为1 ng/ml至10 μ g/ml的不同浓度的吲哚美辛。吲哚美辛降低中国仓鼠卵巢细胞cAMP和前列腺素水平。在高吲哚美辛浓度下，细胞失去了对霍乱毒素或沙门氏菌裂解物刺激的反应能力，同时保留> 95%的活力，如台盼蓝排除法所确定的。前列腺素和cAMP含量的上皮细胞从沙门氏菌的挑战循环中的隐窝上皮细胞组分增加。前列腺素浓度升高，在分离的肠上皮细胞暴露于纯化的霍乱毒素在体外。由上皮细胞合成的前列腺素显然参与实验性霍乱和沙门氏菌病的发病机制。这些数据是一致的肠毒素介导的机制，这两种肠道疾病，并反对炎性细胞的作用，作为源的cAMP和Ephylandins升高出现在肠粘膜实验沙门氏菌病。
Challenge of rabbit intestinal loops with Salmonella typhimurium or Vibrio cholerae resulted in significant elevation of mucosal cAMP and prostaglandin concentrations. This effect could be reproduced in vitro by exposing either isolated epithelial cells from normal rabbits or Chinese hamster ovary cells to purified cholera toxin or cell-free lysates of Salmonella. Indomethacin treatment of animals challenged with Salmonella resulted in less fluid accumulation, in addition to lower concentrations of intestinal cAMP and prostaglandins, compared to that of similarly changed loops in normal animals. Likewise, intestinal loop challenge of indomethacin-treated rabbits with V. cholerae displayed 10-fold higher levels of prostaglandins than tissue from uninfected animals. Prostaglandin levels in Salmonella-infected intestinal loops were similarly elevated, but by only 2- to 3-fold. Chinese hamster ovary cell monolayers were simultaneously exposed to either 10 ng of cholera toxin or 20 .mu.l of Salmonella lysate and varying concentrations of indomethacins ranging from 1 ng/ml to 10 .mu.g/ml. Indomethacin decreased both cAMP and prostaglandin levels in Chinese hamster ovary cells. At high indomethacin concentrations, the cells lost their ability to respond to stimulation with either cholera toxin or Salmonella lysate, while retaining > 95% viability as determined by trypan blue exclusion. The prostaglandin and cAMP content of epithelial cells from Salmonella-challenged loops was increased in crypt epithelial cell fractions. Prostaglandin concentrations were elevated in isolated intestinal epithelial cells exposed to purified cholera toxin in vitro. Prostaglandins synthesized by the epithelial cells apparently are involved in the pathogenesis of both experimental cholera and salmonellosis. The data are consistent with an enterotoxin-mediated mechanism for both diarrheal diseases and argue against the role of inflammatory cells as the source of elevated cAMP and prostaglandins appearing in the intestinal mucosa during experimental salmonellosis.