Expression of apoptotic epithelial cells within lamina propria beneath the basement membrane triggers dextran sulfate sodium-induced colitis.
We postulated that nuclear dust within the lamina propria beneath the basement membrane of the epithelium in colonic mucosa is a form of apoptotic epithelial cells and that its expression triggers dextran sulfate sodium-induced colitis. The aim was to determine the origin of nuclear dust and to explore the correlation between nuclear dust expression and clinicopathologic parameters of colitis. Rats were treated with 3% dextran sulfate sodium. Cells showing double positive staining with cytokeratin and TdT-mediated uUTP-biotin nick-end labeling technique were apoptotic cells derived from epithelial cells. Nuclear dust expression on day 5 correlated with bloody stools and a decrease of mitotic colonic cells just before ulceration. Examination of cultures under light and fluorescent microscopy showed that dextran sulfate sodium caused early apoptosis and late apoptosis or necrosis. Our results suggest that interventions directed toward the apoptotic process may be beneficial in the treatment of ulcerative colitis.
Shichijo
Kazuko
K
Division of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, Japan. shichijo@net.nagasaki-u.ac.jp
Ihara
Makoto
M
Razzaque
Mohammed Shawkat
MS
Matsuu-Matsuyama
Mutsumi
M
Nakayama
Toshiyuki
T
Nakashima
Masahiro
M
Sekine
Ichiro
I
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology*; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology*; D008297:Male; D009092:Mucous Membrane / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016264:Dextran Sulfate