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Unabhängig vom Ort der iNOS Expression ist iNOS-abhängiges NO ein zentraler Vermittler der Entzündungsreaktion im DSS-Colitis Modell der Maus

  • Christian F. Krieglstein
  • K. Stokes
  • J. M. Russel
  • M. B. Grisham
  • N. Senninger
  • D. N. Granger
Conference paper
Part of the Deutsche Gesellschaft für Chirurgie book series (DTGESCHIR, volume 31)

Abstract

Several studies have suggested that iNOS-derived NO may modulate some pathologic changes associated with IBD [1, 2]. The aims were: (1) To examine the importance of inducible nitric oxide (iNOS) expression in the development of experimental colitis and (2) to assess the influence of tissue-specific iNOS expression on neutrophil recruitment in inflamed colons. Study groups included: (A) Wild-type (C57/BL6); (B) WT → WTchimeras with normal iNOS function; (C) WT → iNOS-/- chimeras (produced by bone marrow transplant) with functional blood cell iNOS, but iNOS deficient (-/-) tissue; (D) iNOS-/- → WT chimeras with iNOS deficient blood cells, but normal tissue iNOS activity; and (E) iNOS-deficient mice. Colitis was induced by replacing drinking water with dextran sulphate sodium (DSS) 2.5% over 7 days. Severity of colitis was assessed by a clinical disease activity index (DAI); while colonic injury was quantified using colon length and a histologic damage score. Neutrophil recruitment was indirectly monitored by mesuring colonic myeloperoxidase activity (MPO). In WT mice and WT → WT chimeras, DSS induced colitis was characterized by bloody diarrhea and high DAI values. However, WT → iNOS-/-, iNOS-/- → WT chimeras and iNOS-/- mice exhibited attenuated disease severity with blunted gross rectal bleeding and significantly lower DAI scores. Colon length and histopathology paralleled clinical signs of inflammation. MPO-activity was equally high in WT mice (30.1 ± 1.7) and WT → WT chimeras (29.0 ± 1), whereas MPO-levels in iNOS−/− mice and iNOS−/− → WT chimeras were significantly reduced (9.5 ± 1.7 and 15.6 ± 2.2, respectively). The lowest colonic MPO activity was detected in WT → iNOS−/− chimeras (3.7 ± 0.6). Our findings implicate a role for both blood cell- and tissue-derived NO in the pathogenesis of DSS-induced colitis, with tissue-associated iNOS contributing more significantly to neutrophil recruitment associated with colitis.

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Literatur

  1. 1.
    Kubes P, McCafferty DM (2000) Nitric oxide and intestinal inflammation. Am J Med 109: 150-158PubMedCrossRefGoogle Scholar
  2. 2.
    Krieglstein CF, Cerwinka WH, Laroux FS, Salter JW, Russell JM, Schuermann G, Grisham MB, Ross CR, Granger DN (2001) Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of Superoxide and nitric oxide. J Exp Med 194: 1207- 1218PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2002

Authors and Affiliations

  • Christian F. Krieglstein
    • 1
    • 3
  • K. Stokes
    • 2
  • J. M. Russel
    • 2
  • M. B. Grisham
    • 2
  • N. Senninger
    • 1
  • D. N. Granger
    • 2
  1. 1.Klinik und Poliklinik für Allgemeine Chirurgie, UniversitätsklinikumWestfälische Wilhelms-UniversitätMünsterGermany
  2. 2.Department of Cellular and Molecular PhysiologyLouisiana State University Health Sciences CenterShreveportUSA
  3. 3.Klinik und Poliklinik für Allgemeine Chirurgie, UniversitätsklinikumWestfälische Wilhelms-UniversitätMünsterGermany

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