Background: Crohn's disease (CD) is an inflammatory bowel disease that is associated with several changes in the immune system, including an increased number of infiltrating macrophages. These macrophages release a variety of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) which are critically involved in the onset and the development of CD. The present study was performed to explore the initial involvement of macrophages in the development of T-cell-mediated chronic colitis. Methods: The effects were evaluated of saporin-conjugated anti-CD11b monoclonal antibody (mAb) on the development of chronic colitis in severe combined immunodeficiency (SCID) mice induced by adoptive transfer of CD4+CD45RBhigh T cells as an animal model of CD. Results: Significantly increased CD11b-expressing macrophages as well as CD4+ T cells were found in inflamed colon from colitic mice. Administration of saporin-conjugated anti-CD11b mAb markedly ameliorated the clinical and histopathological disease. In vivo treatment with saporin-conjugated anti-CD11b mAb decreased CD4+ T-cell infiltration in the colon and suppressed inferferon-γ (IFN-γ) and TNF-α production by lamina propria CD4+ T cells. Conclusions: Collectively, the present results suggest an initial role of macrophages in the pathogenesis of T-cell-mediated chronic colitis. Furthermore, the macrophage-specific targeting may be a promising strategy for therapeutic intervention in CD.
|Number of pages||7|
|Journal||Journal of Gastroenterology and Hepatology (Australia)|
|Publication status||Published - 2006 Jul|
- Crohn's disease
- Murine model
ASJC Scopus subject areas