A murine model of granulomatous colitis with mesenteric lymphadenitis induced by mycobacterial cord factor.
Granulomatous colitis is a major entity of human intestinal diseases. We previously reported that intravenous injection of mycobacterial cord factor (CF), a potent macrophage activator, induced pulmonary granulomas in mice with enhanced production of Th1 cytokines and chemokines. In this study we made a murine model of granulomatous colitis by intramural injection of CF. A single dose of 300 microg CF was injected into the wall of the rat and mouse colon in the form of liposomes. After 1 week granulomas developed at the injection site, extending from the subserosa to the lamina propria, and persisted for longer than 6 weeks. They were composed mainly of ED1-positive macrophages, which often underwent apoptosis, and CD4(+) and CD8(+) lymphocytes, which preferentially infiltrated around the macrophage accumulation. Myofibroblast proliferation was not prominent, and no appreciable fibrosis resulted after the decline of granulomas. Although the intestinal epithelium was involved in inflammation, tissue injuries such as mucosal erosion or ulceration were not induced. When granulomas were formed near the Peyer's patches, they invaded deeply into the lymphoid tissue, producing many small islands. The mesenteric lymph nodes also had many granulomatous islands in the cortex and medulla, but the liver and spleen displayed no granulomatous changes, suggesting that liposomal CF spreads via the lymphatic vessels from the injection site. The CF-induced colonic granulomas associated with mesenteric lymphadenitis will be useful for investigating human granulomatous colitis.
Sogawa
Mitsue
M
Department of Anatomy, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. mitsue-s@med.osaka-cu.ac.jp
Matsumoto
Takayuki
T
Yamagami
Hirokazu
H
Yamada
Tamaki
T
Ozeki
Yuriko
Y
Yano
Ikuya
I
Nakajima
Yuji
Y
Arakawa
Tetsuo
T
Kaneda
Kenji
K
D000276:Adjuvants, Immunologic / Q000633:toxicity*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003311:Cord Factors / Q000633:toxicity*; D003424:Crohn Disease / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008640:Mesenteric Lymphadenitis / Q000209:etiology / Q000473:pathology*; D009161:Mycobacterium / Q000276:immunology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D003311:Cord Factors; D008081:Liposomes