Die mesenterialen Lymphknoten und das GALT spielen eine zentrale Rolle bei der Vermittlung des gastrointestinalen Field Effects

Abstract

Introduction: Localized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we have demonstrated this gastrointestinal field effect (FE) in rodent models. We showed IM-mediated recruitment of DC into the small bowel muscularis and mesenteric lymph nodes combined with upregulation of costimulatory immuno-competent molecules in DCs. Furthermore, we could show a central involvement of DC in the FE. The aim of this study was to investigate the role of mesenteric lymph nodes (MLN) and GALT in FE postulated as immunologically mediated. Methods: Mice underwent standardized IM or sham operation and tissues (small bowel muscularis, colonic muscularis, mesenteric lymph nodes) were obtained at different times after IM. The FE was analysed by measuring the gastrointestinal transit time or muscularis contractility in wildtype mice (WT) versus mice after mesenteric lymphadenectomy (LAD), versus lymphatic tissue knockout mice, and versus mice treated with lymphocyte-depleting drugs. Furthermore, expression of inflammation markers and of adhesion molecules was determined by Taqman-PCR. Results: Both the mesenteric lymphadenectomy and the lack of lymphoid tissue significantly reduced the FE after IM as compared to WT. Concomittantly, we observed a significant down-regulation of inflammation markers in intestinal and colonic muscularis of those mice compared to WT. In the immunohistologically stained specimen of the colonic muscularis we found a lower amount of inflammatoric cells both in LAD-mice and in lymphatic tissue KO-mice. The same results were obtained in mice treated by drug mentioned above. Conclusion: Immune mechanisms contribute to FE. The FE is obviously mediated by lymph cells of the gut and the mesenteric lymph nodes.