Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice.
OBJECTIVE
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.
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands. w.j.dejonge@amc.uva.nl
Wouter J
WJ
de Jonge
Frans O
FO
The
Dennis
D
van der Coelen
Roelof J
RJ
Bennink
Pieter H
PH
Reitsma
Sander J
SJ
van Deventer
René M
RM
van den Wijngaard
Guy E
GE
Boeckxstaens
D000005:Abdomen / Q000601:surgery*; D000818:Animals; D015550:Cell Degranulation / Q000276:immunology*; D004751:Enteritis / Q000276:immunology / Q000378:metabolism; D005260:Female; D045823:Ileus / Q000276:immunology* / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D011183:Postoperative Complications / Q000276:immunology / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics
D019009:Proto-Oncogene Proteins c-kit