Mast cell activation within the mesentery depends on vagal signaling following abdominal surgery

Introduction Abdominal surgery causes an inflammatory reaction in the intestines, resulting in a postoperative ileus. Mast cells can be divided into mucosal mast cells and connective tissue mast cells. In this study, we investigated mast cell activation within the gastrointestinal tract during abdominal surgery and explored the activation and role of connective tissue mast cells in postoperative ileus. Material and Methods Postoperative ileus was induced in wild-type, Mcpt5-Cre xDTRfl/fl and Mcpt5-Cre mice by intestinal manipulation. In vitro, vagal activation was further specified by stimulating mast cells with substance P, nicotine and bethanechol. Mast cell degranulation in the mesentery and stomach wall was visualized using avidin staining. Vagal requirement was assessed by performing unilateral cervical vagotomy prior intestinal manipulation. The role of macrophages was investigated by macrophage depletion before surgery. Intestinal inflammation was evaluated by analyzing leukocyte influx into the intestine, and motility was analyzed by a gastrointestinal transit after surgery. Results Surgery induced mast cell degranulation within mesentery. Mast cell degranulation was independent of macrophage activity or mechanical stress, whereas vagotomy prevented mast cell activation in vivo. In vitro, mast cell degranulation was triggered by muscarinic acetylcholine receptors, but not by nicotinic receptors. However, Mcpt5-Cre DTRfl/fl mice showed no alteration in leukocyte influx into the muscularis externa or gastrointestinal transit compared to controls. Conclusions In conclusion, mast cell activation in the mesentery is induced via muscarinic acetylcholine receptors after surgery. However, depletion of these mast cells did not alter postoperative ileus in mice, suggesting that mast cells do not play a direct role in the pathogenesis of postoperative ileus.