Neuro-modulation of ion secretion by inflammatory mediators.
Neuro-modulation of ion secretion by inflammatory mediators.
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炎症介质对离子分泌的神经调节。
DOI：
10.1111/j.1749-6632.1992.tb39773.x
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发表时间：
1992
影响因子：
5.2
通讯作者：
Cooke,HJ
中科院分区：
文献类型：
--
作者：
Cooke,HJ
保护宿主免受肠腔内大量微生物的侵害。肠上皮的完整性、粘液的分泌（与分泌型伊加结合）、由正常肠道植物群产生的抗微生物代谢物的存在、水肿和可能的液体分泌都阻碍肠道病原体的进入和传播。上皮屏障的破坏和抗原的摄取触发导致IgE或IgG产生的免疫应答。抗体通过与其表面上的Fc受体结合长达数月的时间使局部肥大细胞敏化。肥大细胞在肠道与外部环境的界面处具有重要的免疫调节功能。用抗原激发致敏肠是一种I型超敏反应，其由占据肥大细胞上Fc受体的抗体交联和随后释放介质引起。这激活了肠道效应系统，导致大量分泌和改变的运动模式，其协调以清除肠腔的内容物，可能导致产生腹泻状态。4肥大细胞对免疫刺激的反应是释放预先形成的和新合成的物质。影响离子转运的可溶性介质包括组胺、白藜芦醇、白三烯、腺苷、5-羟色胺等。2本文将重点讨论这些肥大细胞介质在分泌反应放大中的相互作用。分泌的增强可以在几个水平上发生：1）肥大细胞介质可以刺激上皮细胞内不同的信号转导途径和第二信使以增强彼此的信号转导途径和第二信使; 2）在上皮细胞水平上，肥大细胞介质可以增强从粘膜下层/固有层内的免疫细胞或间充质细胞释放的其他中间信使的作用;（2）肥大细胞介导物可增加神经元的兴奋性，导致神经递质的释放，从而增强上皮细胞对介导物的反应。为了研究肥大细胞介质与肠神经系统和上皮细胞的相互作用，我的实验室使用了两种模型。这些包括旋毛虫寄生宿主和牛乳致敏豚鼠。在前一种模型中，豚鼠通过口服接种2 × 103旋毛虫幼虫进行免疫，并在6-8周后处死。3-4结肠组织在体外用来自感染性旋毛虫a的体细胞蛋白抗原进行攻击。这项工作得到了国立卫生研究院赠款R 01-DK 37240和R 01-DK 37237以及俄亥俄州州立大学赠款B/A 222157的支持。
The host is protected from the multitude of microorganisms presiding within the intestinal lumen. The integrity of the intestinal epithelium, secretion of mucus (in combination with secretory IgA), the presence of antimicrobial metabolites produced by normal enteric flora, peristalsis and possibly secretion of fluid all impede the entry and dissemination of enteric pathogens. Disruption of the epithelial barrier and uptake of antigen triggers an immune response which results in production of IgE or IgG,.'v2 The antibodies sensitize local mast cells by binding to Fc receptors on their surface for periods as long as several months.'Mast cells have important immunoregulatory functions at the interface of the intestine with the external environment. Challenge of sensitized intestine with antigen elicits a type I hypersensitivity reaction that results from crosslinking the antibodies occupying Fc receptors on mast cells and the consequent release of mediators. This activates intestinal effector systems resulting in profuse secretion and altered motility patterns which are coordinated to clear the intestinal lumen of its contents with a possible consequence of producing a diarrheal state. 4 Preformed and newly synthesized substances are released from mast cells in response to immunologic stimuli. Soluble mediators that affect ion transport include histamine, prostaglandins, leukotrienes, adenosine, 5-hydroxytryptamine and others. 2 This paper will focus on the interactions of a few of these mast cell mediators in amplification of secretory responses. Augmentation of secretion can occur at several levels: 1) Mast cell mediators may stimulate different signal transduction pathways and second messengers within epithelial cells to enhance each other's 2) At the level of the epithelial cell, mast cell mediators may augment the actions of other intermediary messengers released from immunocytes or mesenchymal cells within the submucosa/lamina propria; 2 3) Mast cell mediators may increase neuronal excitability resulting in release of neurotransmitters which could augment the epithelial responses to the mediators.'To study interactions of mast cell mediators with the enteric nervous system and the epithelium, two models have been used in my laboratory. These include the Trichinella spiralis parasitized host, and bovine milk-sensitized guinea pigs. In the former model, guinea pigs are immunized by oral inoculation with 2 x lo3 Trichinella spiralis larvae and sacrificed 6-8 weeks later. 3-4 Colonic tissues are challenged in vitro with a somatic protein antigen derived from infective Trichinella a This work was supported by National Institutes of Health Grants R01-DK37240 and R01-DK37237 and by the Ohio State University Grant B/A 222157.