Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant
We induced granulomatous enterocolitis in rabbits by injecting them with muramyl dipeptide (MDP), a subunit of the peptidoglycan polymers that endow the bacterial cell wall with structural rigidity, emulsified with Freund's incomplete adjuvant (FIA). Injections of 0.1ml of a water-in-oil emulsion of MDP and FIA were given submucosally at six sites in the rectum and colon, 10cm proximal to the anus, using a flexible endoscope. Four rabbits each were sacrificed 1, 2, and 4 weeks after a single injection of the emulsion. Another 4 rabbits each were injected six times at 1-and 2-weeks intervals, and were sacrificed 1 and 2 weeks after the last injection of the emulsion, respectively. In all 20 rabbits, injected with the MDP emulsion, histological findings of the colon consisted of cellular infiltrations of plasma cells and lymphocytes, granulomatous lesions, and granulomas, although the findings differed in degree. Cellular infiltration in hyperplastic villi and denuded epithelia of the small intestine were seen in 2 of 8 rabbits repeated that received MDP emulsion injections. The histological changes in this animal model may be useful for studying the pathogenesis of inflammatory bowel disease in humans.
Key wordsmuramyl dipeptide bacterial cell wall Freund's incomplete adjuvant epithelioid granuloma rabbit granulomatous enterocolitis
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- 3.Kent TH, Cardelli RM, Stamler FW. Small intestinal ulcers and intestinal flora in rats given indomethacin. Am J Pathol 1969; 34:237–249.Google Scholar
- 8.Emori K, Tanaka A. Granuloma formation by synthetic bacteria cell wall fragment: Muramyl dipeptide. Infect Immunol 1978; 19:613–620.Google Scholar
- 10.Emori K, Nagao S, Shigematsu N, et al. Granuloma formation by muramyl dipeptide associated with branched fatty acids, a structure probably essential for tubercle formation by mycobacterium tuberculosis. Infect Immunol 1985;49:244–249.Google Scholar
- 14.Ogawa T, Kotani S, Kusumoto S, et al. Possible chemotaxis of human monocytes by N-acetylmuramyl-L-alanyl-D-isoglutamine. Infect Immunol 1983;39:449–451.Google Scholar
- 15.Wakasa H, Ishikawa H, Asano S. Experimental granuloma formation by the injection of MDP into the intestinal wall (in Japanese). In: Shiratori T (ed) Annual of achievements in 1982 by IBD study groups in the Ministry of Health and Welfare of Japan. Nara 1983;260–263.Google Scholar