Immunopathogenesis of Experimental Ulcerative Colitis is Mediated by Eosinophil Peroxidase

Elizabeth Forbes, Tosei Murase, Ming Yang, Klaus I. Matthaei, James J. Lee, Nancy A. Lee, Paul S. Foster, Simon P. Hogan

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

The precise role that individual inflammatory cells and mediators play in the development of gastrointestinal (GI) dysfunction and extraintestinal clinical manifestations of ulcerative colitis (UC) is unknown. In this study, we have used a mouse model of UC to establish a central role for eotaxin and, in turn, eosinophils in the development of the immunopathogenesis of this disease. In this model the administration of dextran sodium sulfate (DSS) induces a prominent colonic eosinophilic inflammation and GI dysfunction (diarrhea with blood and shortening of the colon) that resembles UC in patients. GI dysfunction was associated with evidence of eosinophilic cytolytic degranulation and the release of eosinophil peroxidase (EPO) into the colon lumen. By using IL-5 or eotaxin-deficient mice, we show an important role for eotaxin in eosinophil recruitment into the colon during experimental UC. Furthermore, using EPO-deficient mice and an EPO inhibitor resorcinol we demonstrate that eosinophil-derived peroxidase is critical in the development of GI dysfunction in experimental UC. These findings provide direct evidence of a central role for eosinophils and EPO in GI dysfunction and potentially the immunopathogenesis of UC.

Original languageEnglish (US)
Pages (from-to)5664-5675
Number of pages12
JournalJournal of Immunology
Volume172
Issue number9
DOIs
StatePublished - May 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Immunopathogenesis of Experimental Ulcerative Colitis is Mediated by Eosinophil Peroxidase'. Together they form a unique fingerprint.

  • Cite this

    Forbes, E., Murase, T., Yang, M., Matthaei, K. I., Lee, J. J., Lee, N. A., Foster, P. S., & Hogan, S. P. (2004). Immunopathogenesis of Experimental Ulcerative Colitis is Mediated by Eosinophil Peroxidase. Journal of Immunology, 172(9), 5664-5675. https://doi.org/10.4049/jimmunol.172.9.5664