Mast cell-mediated colonic immune function and its inhibition by dietary aspirin in mice infected with Trichinella spiralis.
Mast cell-mediated colonic immune function and its inhibition by dietary aspirin in mice infected with Trichinella spiralis.
复制标题
旋毛虫感染小鼠中肥大细胞介导的结肠免疫功能及其饮食阿司匹林的抑制作用。
DOI：
10.1159/000236815
复制
发表时间：
1994
影响因子：
2.8
通讯作者：
Castro,GA
中科院分区：
文献类型：
--
作者：
Broaddus,RR;Castro,GA
由于肠壁细胞成分的整合性，对局部粘膜免疫系统及其适应能力的了解应该可以为炎症性肠道疾病和结直肠癌等结肠疾病提供更多见解。为了建立一种原位定量结肠粘膜免疫功能的方法，在感染旋毛虫的小鼠结肠中测定了由I型超敏反应介导的离子转运。将致敏的远端结肠段固定在Ussing室中，并用T.螺旋体衍生抗原导致短路电流（ΔIsc）升高，该电流具有抗原特异性，并被呋塞米抑制。来自感染的肥大细胞缺陷W/Wv小鼠的结肠段对T的攻击无反应。螺旋体抗原用各种药物抑制过敏性介质，表明野牡丹素和白三烯是抗原诱导的ΔIsc的主要介质，5-HT也起作用。神经阻滞与河豚毒素或阻断组胺H1受体与苯海拉明未能抑制结肠免疫反应。来自随意喂食含阿司匹林饮食（800 mg/kg粉状饮食）6周的免疫小鼠的远端结肠对抗原的应答降低。然而，阿司匹林对空肠中抗原诱导的Δ Isc或远端结肠中Cl-促分泌素刺激的Δ Isc没有影响。这些结果表明，花生四烯酸代谢产物是T免疫小鼠远端结肠中肥大细胞依赖的、抗原刺激的Cl-分泌的重要介质。螺旋形的此外，饮食中的阿司匹林对免疫介导的远端结肠和空肠的离子转运有不同的影响，这表明不同部位的粘膜免疫功能可以优先用于药理学调节。
Because of the integrated nature of cellular elements in the gut wall, an understanding of the local mucosal immune system and its adaptive capacity should provide more insight into diseases of the colon, such as inflammatory bowel disease and colorectal cancer. To develop a method to quantify colonic mucosal immune function in situ, ion transport mediated by a type I hypersensitivity reaction was measured in the colon of mice infected withTrichinella spiralis. Segments of sensitized distal colon mounted in Ussing chambers and challenged withT. spiralis-derived antigen resulted in a rise in short-circuit current (ΔIsc) that was antigen-specific and inhibited by furosemide. Colonic segments from infected, mast cell-deficient W/Wvmice were unresponsive to challenge withT. spiralisantigen. Inhibition of anaphylactic mediators with various pharmacological agents implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced ΔIsc, with 5-HT also playing a role. Neural blockade with tetrodotoxin or blockade of histamine H1receptors with diphen-hydramine failed to inhibit the colonic immune response. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 weeks had a decreased response to antigen. However, dietary aspirin had no effect on antigen-induced ΔIscin the jejunum or on Cl––secretagogue-stimulated ΔIscin the distal colon. These results suggest that products of arachidonic acid metabolism are important mediators of mast cell-dependent, antigen-stimulated Cl––secretion in the distal colon of mice immunized by infection withT. spiralis. Furthermore, dietary aspirin has differential effects on immune-mediated ion transport of the distal colon and jejunum, suggesting that mucosal immune function at different sites can be preferentially targeted for pharmacological modulation.