title: Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. taka.gast@tmd.ac.jp
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
authors.forename: Koji
authors.initials: K
authors.lastname: Uraushihara
authors.forename: Teruji
authors.initials: T
authors.lastname: Totsuka
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nemoto
authors.forename: Rei
authors.initials: R
authors.lastname: Fujii
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawamura
authors.forename: Shin
authors.initials: S
authors.lastname: Makita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawada
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Mamoru
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D039481:CD11b Antigen / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D028321:Plant Preparations / Q000494:pharmacology; D029750:Saponaria; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D028321:Plant Preparations; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma