Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice.

Abstract

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.

• Authors: Wouter J de Jonge, Frans O The, Dennis van der Coelen, Roelof J Bennink, Pieter H Reitsma, Sander J van Deventer, René M van den Wijngaard, Guy E Boeckxstaens
• Journal: Gastroenterology (Gastroenterology) Vol. 127 Issue 2 Pg. 535-45 (Aug 2004) ISSN: 0016-5085 [Print] United States
• PMID: 15300586 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-kit

Topics

• Abdomen (surgery)
• Animals
• Cell Degranulation (immunology)
• Enteritis (immunology, metabolism)
• Female
• Ileus (immunology, metabolism)
• Leukocytes (immunology)
• Mast Cells (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Mutant Strains
• Postoperative Complications (immunology, metabolism)
• Proto-Oncogene Proteins c-kit (genetics)