Ameliorating effect of saporin-conjugated anti-CD11b monoclonal antibody in a murine T-cell-mediated chronic colitis.
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.
Kanai
Takanori
T
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. taka.gast@tmd.ac.jp
Uraushihara
Koji
K
Totsuka
Teruji
T
Nemoto
Yasuhiro
Y
Fujii
Rei
R
Kawamura
Takahiro
T
Makita
Shin
S
Sawada
Daisuke
D
Yagita
Hideo
H
Okumura
Ko
K
Watanabe
Mamoru
M
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
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D028321:Plant Preparations; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma