Koscielny A, Boerner T, Wehner S, Kurts C, Kalff J C
Department of Surgery, University of Bonn Medical School, Sigmund-Freud-Strasse 25, D-53125 Bonn, Germany.
Transplant Proc. 2006 Jul-Aug;38(6):1815-7. doi: 10.1016/j.transproceed.2006.06.087.
Intestinal manipulation leads to local bowel wall inflammation that subsequently spreads over the entire gastrointestinal tract. Previously, this gastrointestinal field effect had been demonstrated by us in a rodent model. We herein postulated an immunologic mechanism mediated by activated leukocytes. The aim of this study was to investigate the activation, maturation and migration of dendritic cells (DC) of the intestinal smooth muscle following surgical trauma and i.p. lipopolysaccharide challenge.
Mice underwent standardized intestinal manipulation or iP LPS administration and tissues (intestinal muscularis, Peyer's patches, mesenteric lymph nodes, and spleen) were obtained at various times after manipulation. DC were isolated by tissue digestion and separated by CD11c-iMAG. The harvested DC were analyzed by FACS. The activation pattern of DC was analyzed by polymerase chain reaction.
We found a significant increase in DC within the intestinal muscularis, the Peyer's patches and the mesenteric lymph nodes at 6 and 12 hours following intestinal manipulation and injection of LPS. There was an upregulation of the costimulatory molecules major histocompatibility complex II, CD40, CD80, CD86, and CD205 in the DC after intestinal manipulation. CCR-2, CCR-5, CCR-7, CCL-19, and interleukin-12a were upregulated in a time- and tissue-dependent manner.
Intestinal manipulation or LPS challenge induced a recruitment of DC into the muscularis externa and mesenteric lymph nodes combined with an upregulation of costimulatory immunocompetent molecules and migratory surface markers in DCs. These findings demonstrate a precondition for an immunologic response and a possible immunologically mediated gastrointestinal field effect.
肠道操作会导致局部肠壁炎症，随后炎症会扩散至整个胃肠道。此前，我们已在啮齿动物模型中证实了这种胃肠道场效应。我们在此推测这是一种由活化白细胞介导的免疫机制。本研究的目的是调查手术创伤和腹腔注射脂多糖刺激后，肠道平滑肌中树突状细胞（DC）的活化、成熟和迁移情况。
对小鼠进行标准化肠道操作或腹腔注射脂多糖，在操作后的不同时间获取组织（肠肌层、派尔集合淋巴结、肠系膜淋巴结和脾脏）。通过组织消化分离DC，并利用CD11c-iMAG进行分离。收获的DC通过流式细胞术进行分析。通过聚合酶链反应分析DC的活化模式。
我们发现，在肠道操作和注射脂多糖后的6小时和12小时，肠肌层、派尔集合淋巴结和肠系膜淋巴结中的DC显著增加。肠道操作后，DC中协同刺激分子主要组织相容性复合体II、CD40、CD80、CD86和CD205上调。CCR-2、CCR-5、CCR-7、CCL-19和白细胞介素-12a以时间和组织依赖性方式上调。
肠道操作或脂多糖刺激诱导DC募集至肌层外膜和肠系膜淋巴结，同时DC中协同刺激免疫活性分子和迁移表面标志物上调。这些发现证明了免疫反应的一个前提条件以及一种可能的免疫介导的胃肠道场效应。
