Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2005; 11(29): 4505-4510
Published online Aug 7, 2005. doi: 10.3748/wjg.v11.i29.4505
Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats
Kazuko Shichijo, Kazuya Makiyama, Chun-Yang Wen, Mutsumi Matsuu, Toshiyuki Nakayama, Masahiro Nakashima, Makoto Ihara, Ichiro Sekine
Kazuko Shichijo, Chun-Yang Wen, Mutsumi Matsuu, Toshiyuki Nakayama, Ichiro Sekine, Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Kazuya Makiyama, Department of Endoscopy, Nagasaki University School of Medicine Hospital and Clinics, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Chun-Yang Wen, Department of Digestive Disease, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
Masahiro Nakashima, Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Makoto Ihara, Radiation Biophysics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan
Author contributions: All authors contributed equally to the work.
Supported by a grant-in-aid from the Ministry of Science, Education, Sports and Culture of Japan, No. 14570193
Correspondence to: Kazuko Shichijo, PhD, Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. shichijo@net.nagasaki-u.ac.jp
Telephone: +81-95-849-7107 Fax: +81-95-849-7108
Received: October 25, 2004
Revised: December 20, 2004
Accepted: December 23, 2004
Published online: August 7, 2005
Abstract

AIM: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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).

Keywords: Ulcerative colitis, Eosinophil cationic protein, Dextran sulfate sodium