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Journal of Gastroenterology

, Volume 30, Issue 4, pp 472–477 | Cite as

Rabbit granulomatous enterocolitis induced by injection of muramyl dipeptide emulsified with Freund's incomplete adjuvant

  • Kiyoo Kuroe
  • Yoichi Haga
  • Osamu Funakoshi
  • Ichiro Mizuki
  • Kosuke Kanazawa
  • Yutaka Yoshida
Alimentary Tract

Abstract

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 words

muramyl dipeptide bacterial cell wall Freund's incomplete adjuvant epithelioid granuloma rabbit granulomatous enterocolitis 

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References

  1. 1.
    Morris GP, Beck PL, Herridge MS, et al. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989;96:795–803.PubMedGoogle Scholar
  2. 2.
    Watt J, Marcus R. Carrageenan-induced ulceration of the large intestine in the guinea pig. Gut 1971;12:164–171.PubMedGoogle Scholar
  3. 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
  4. 4.
    Stewart THM, Hetenyi C, Rowsell H, Orizaga M. Ulcerative enterocolitis in dogs induced by drugs. J Pathol 1980;131:363–378.CrossRefPubMedGoogle Scholar
  5. 5.
    Némirovsky MS, Hugon JS. Immunopathology of guinea pig autoimmune enterocolitis induced by alloimmunisation with an intestinal protein. Gut 1986;27:1434–1442.PubMedGoogle Scholar
  6. 6.
    Sartor RB, Cromartie WJ, Powell DW, et al. Granulomatous enterocolitis induced in rats by purified bacterial cell wall fragments. Gastroenterology 1985;89:587–595.PubMedGoogle Scholar
  7. 7.
    Yamada T, Sartor RB, Marshall S, et al. Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats. Gastroenterology 1993;104:759–771.PubMedGoogle Scholar
  8. 8.
    Emori K, Tanaka A. Granuloma formation by synthetic bacteria cell wall fragment: Muramyl dipeptide. Infect Immunol 1978; 19:613–620.Google Scholar
  9. 9.
    Tanaka A, Emori K. Epthelioid granuloma formation by a synthetic bacterial cell wall component, muramyl dipeptide (MDP). Am J Pathol 1980;98:733–748.PubMedGoogle Scholar
  10. 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
  11. 11.
    Carter RL, Jamison DG, Vollum RL. Histological changes evoked in mice by Freund's incomplete adjuvant. J Pathol Bact 1968;95:471–476.CrossRefGoogle Scholar
  12. 12.
    Yamanaka M, Hiramatsu K, Hirahara T, et al. Pathological studies on local tissue reactions in guinea pigs and rats caused by four different adjuvants. J Vet Med Sci 1992;54:685–692.PubMedGoogle Scholar
  13. 13.
    Goto N. Comparative studies on effects of incomplete oil adjuvants with different physical properties. Jpn J Med Sci Biol 1978;31:53–79.PubMedGoogle Scholar
  14. 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. 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

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Kiyoo Kuroe
    • 1
  • Yoichi Haga
    • 1
  • Osamu Funakoshi
    • 1
  • Ichiro Mizuki
    • 1
  • Kosuke Kanazawa
    • 1
  • Yutaka Yoshida
    • 1
  1. 1.First Department of Internal MedicineHirosaki University School of MedicineAomoriJapan

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