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


CONCLUSIONS
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).
Shichijo
Kazuko
K
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
Makiyama
Kazuya
K
Wen
Chun-Yang
CY
Matsuu
Mutsumi
M
Nakayama
Toshiyuki
T
Nakashima
Masahiro
M
Ihara
Makoto
M
Sekine
Ichiro
I
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000925:Anticoagulants; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000517:prevention & control* / Q000628:therapy*; D016264:Dextran Sulfate; D047150:Eosinophil Cationic Protein / Q000737:chemistry / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar
D000906:Antibodies; D000925:Anticoagulants; D016264:Dextran Sulfate; D047150:Eosinophil Cationic Protein