Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis

Takanori Kanai, Koji Uraushihara, Teruji Totsuka, Yasuhiro Nemoto, Rei Fujii, Takahiro Kawamura, Shin Makita, Daisuke Sawada, Hideo Yagita, Ko Okumura, Mamoru Watanabe

Research output: Contribution to journalArticle

13 Citations (Scopus)

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-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.

Original languageEnglish
Pages (from-to)1136-1142
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume21
Issue number7
DOIs
Publication statusPublished - 2006 Jul
Externally publishedYes

Keywords

  • Crohn's disease
  • Macrophages
  • Murine model
  • Targeting
  • Therapy

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Kanai, T., Uraushihara, K., Totsuka, T., Nemoto, Y., Fujii, R., Kawamura, T., Makita, S., Sawada, D., Yagita, H., Okumura, K., & Watanabe, M. (2006). Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis. Journal of Gastroenterology and Hepatology (Australia), 21(7), 1136-1142. https://doi.org/10.1111/j.1440-1746.2006.04391.x