Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice

Gastroenterology. 2004 Aug;127(2):535-45. doi: 10.1053/j.gastro.2004.04.017.


Background & aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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


  • Proto-Oncogene Proteins c-kit