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  • Title: Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.
    Author: Kanai T, Uraushihara K, Totsuka T, Nemoto Y, Fujii R, Kawamura T, Makita S, Sawada D, Yagita H, Okumura K, Watanabe M.
    Journal: J Gastroenterol Hepatol; 2006 Jul; 21(7):1136-42. PubMed ID: 16824065.
    Abstract:
    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-alpha (TNF-alpha) 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(+)CD45RB(high) 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 interferon-gamma (IFN-gamma) and TNF-alpha 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.
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