Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 127; no. 2; pp. 535 - 545
• Main Authors: de Jonge, Wouter J, The, Frans O, van der Coelen, Dennis, Bennink, Roelof J, Reitsma, Pieter H, van Deventer, Sander J, van den Wijngaard, René M, Boeckxstaens, Guy E
• Format: Journal Article
• Language: English
• Published: United States 01-08-2004
• Subjects: Abdomen - surgery; Animals; Cell Degranulation - immunology; Enteritis - immunology; Enteritis - metabolism; Female; Ileus - immunology; Ileus - metabolism; Leukocytes - immunology; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Mice, Mutant Strains; Postoperative Complications - immunology; Postoperative Complications - metabolism; Proto-Oncogene Proteins c-kit - genetics
• ISSN: 0016-5085
• DOI: 10.1053/j.gastro.2004.04.017

Inflammation of the intestinal muscularis following manipulation during surgery plays a crucial role in the pathogenesis of postoperative ileus. Here, we evaluate the role of mast cell activation in the recruitment of infiltrates in a murine model.
Twenty-four hours after control laparotomy or intestinal manipulation, gastric emptying was determined. Mast cell degranulation was determined by measurement of mast cell protease-I in peritoneal fluid. Intestinal inflammation was assessed by determination of tissue myeloperoxidase activity and histochemical staining.
Intestinal manipulation elicited a significant increase in mast cell protease-I levels in peritoneal fluid and resulted in recruitment of inflammatory infiltrates to the intestinal muscularis. This infiltrate was associated with a delay in gastric emptying 24 hours after surgery. Pretreatment with mast cell stabilizers ketotifen (1 mg/kg, p.o.) or doxantrazole (5 mg/kg, i.p.) prevented both manipulation-induced inflammation and gastroparesis. Reciprocally, in vivo exposure of an ileal loop to the mast cell secretagogue compound 48/80 (0.2 mg/mL for 1 minute) induced muscular inflammation and delayed gastric emptying. The manipulation-induced inflammation was dependent on the presence of mast cells because intestinal manipulation in mast cell-deficient Kit/Kitv mice did not elicit significant leukocyte recruitment. Reconstitution of Kit/Kitv mice with cultured bone marrow-derived mast cells from congenic wild types restored the manipulation-induced inflammation.
Our results show that degranulation of connective tissue mast cells is a key event for the establishment of the intestinal infiltrate that mediates postoperative ileus following abdominal surgery.