Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

Abstract

To produce an antibody against rat eosinophil cationic protein (ECP) and to examine the effects of the antibody in rats with dextran sulfate sodium (DSS)-induced colitis. An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms (diarrhea and/or blood-stained stool). Body weight gain was significantly greater and the colon length was significantly longer in anti-ECP-treated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor (MIF) in anti-ECP-treated rats. Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis (UC).