Development of dextran sulfate sodium-induced colitis is aggravated in mice genetically deficient for complement C5.
The complement system is a potent effector of innate immunity. To elucidate the pathophysiological role of the complement system in inflammatory bowel disease (IBD), we evaluated the development of dextran sulfate sodium (DSS)-induced colitis in genetically complement C5-deficient mice. We used DBA2/J mice, which are genetically deficient in complement C5. DBA1/J mice have a normal complement system, and were used as controls. Experimental colitis was induced by the oral administration of 3.5% (w/v) DSS in their drinking water for 10 days. On day 10, all mice were sacrificed and their colons were collected. The development of colitis was assessed by the histological score, disease activity index, myeloperoxidase (MPO) activity, and macroscopic changes of the colon. Body weight loss was more apparent in the DBA2/J mice than in control DBA1/J mice. The colon length was shorter in the DBA2/J mice than in DBA1/J mice. The disease activity index, histological colitis score, and MPO activity were all significantly higher in the DBA2/J mice than in DBA1/J mice. Microscopically, mucosal edema, cellular infiltration and disruption of the epithelium were much more severe in the DBA2/J mice than in DBA1/J mice. The development of DSS colitis was aggravated in genetically C5-deficient DBA2/J mice. These findings suggest that the complement system might play a protective role in the development of DSS-induced experimental colitis.
Deguchi
Yasuyuki
Y
Department of Internal Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu 520-2192, Japan.
Andoh
Akira
A
Inatomi
Osamu
O
Araki
Yoshio
Y
Hata
Kazunori
K
Tsujikawa
Tomoyuki
T
Kitoh
Katsuyuki
K
Fujiyama
Yoshihide
Y
D000818:Animals; D001835:Body Weight / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003182:Complement C5 / Q000172:deficiency / Q000235:genetics*; D016264:Dextran Sulfate / Q000008:administration & dosage / Q000633:toxicity; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors
D003182:Complement C5; D016264:Dextran Sulfate; D009195:Peroxidase