Role of neutrophils in cerulein-induced pancreatitis in rats: possible involvement of apoptosis.
We investigated the role of neutrophils and the involvement of apoptosis in cerulein-induced acute pancreatitis. Male Sprague-Dawley rats were divided into 2 groups. In the control group, acute pancreatitis was induced by subcutaneous injections of cerulein. In methotrexate-treated group, the rats received intraperitoneal injections of methotrexate to produce neutrophil depletion before the injections of cerulein. The rats were sacrificed at the indicated time points until 72 h after the first injection of cerulein. Neutrophil depletion ameliorated pancreatic edema and vacuole formation in acinar cells during the early stages of cerulein-induced acute pancreatitis. Electron microscopy, DNA gel electrophoresis and in situ nick end-labeling revealed the involvement of apoptosis in acinar cells in cerulein-induced acute pancreatitis. Furthermore, the number of apoptotic acinar cells in neutrophil-depleted rats showed an about 2-fold increase during the late stages when compared with those in the control rats. Our results suggest that neutrophil depletion in cerulein-induced pancreatitis leads to amelioration of pancreatic injury during the early stage, and enhancement of apoptosis by neutrophil depletion occurs during the late stage.
Fujimoto
K
K
First Department of Surgery, Kyoto University, Japan.
Hosotani
R
R
Doi
R
R
Wada
M
M
Lee
J U
JU
Koshiba
T
T
Miyamoto
Y
Y
Imamura
M
M
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis; D002108:Ceruletide; D008049:Lipase / Q000097:blood; D008297:Male; D008727:Methotrexate; D008854:Microscopy, Electron; D009503:Neutropenia / Q000139:chemically induced; D009504:Neutrophils / Q000502:physiology*; D010179:Pancreas / Q000201:enzymology / Q000473:pathology*; D010195:Pancreatitis / Q000139:chemically induced* / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002108:Ceruletide; D009195:Peroxidase; D008049:Lipase; D000681:Amylases; D008727:Methotrexate