The Role of Dendritic Cells in the Gastrointestinal Field Effect

Abstract

Introduction 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. Methods 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. Results 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. Conclusion 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.