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Ameliorating effect of saporin‐conjugated anti‐CD11b monoclonal antibody in a murine T‐cell‐mediated chronic colitis
Author(s) -
Kanai Takanori,
Uraushihara Koji,
Totsuka Teruji,
Nemoto Yasuhiro,
Fujii Rei,
Kawamura Takahiro,
Makita Shin,
Sawada Daisuke,
Yagita Hideo,
Okumura Ko,
Watanabe Mamoru
Publication year - 2006
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04391.x
Subject(s) - medicine , colitis , monoclonal antibody , inflammatory bowel disease , immunology , tumor necrosis factor alpha , immune system , adoptive cell transfer , saporin , lamina propria , t cell , integrin alpha m , interferon gamma , antibody , pathology , immunotoxin , disease , epithelium
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 + 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 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.