Mast cell degranulation during abdominal surgery initiates postoperative ileus in mice
| Autor: | 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 |
|---|---|
| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology, Clinical Immunology and Rheumatology, AII - Amsterdam institute for Infection and Immunity, CCA -Cancer Center Amsterdam, Nuclear Medicine, Other departments, Extramural researchers, Center of Experimental and Molecular Medicine |
| Rok vydání: | 2004 |
| Předmět: |
Ketotifen
Pathology medicine.medical_specialty Connective tissue Inflammation Cell Degranulation Mice chemistry.chemical_compound Ileus Postoperative Complications Abdomen Leukocytes medicine Animals Mast Cells Mice Inbred BALB C Hepatology Gastric emptying business.industry Peritoneal fluid Gastroenterology Degranulation Compound 48/80 Mast cell Enteritis Mice Mutant Strains Proto-Oncogene Proteins c-kit medicine.anatomical_structure chemistry Female medicine.symptom business medicine.drug |
| Zdroj: | Gastroenterology, 127(2), 535-545. W.B. Saunders Ltd |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/j.gastro.2004.04.017 |
| Popis: | 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, PO) or doxantrazole (5 mg/kg, IP) 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. |
| Databáze: | OpenAIRE |
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