Role of Neutrophils in Cerulein-Induced Pancreatitis in Rats: Possible Involvement of Apoptosis

Abstract

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.

Pathophysiology of acute pancreatitis

“…Sandoval et al [47] have reported a dramatic increase in apoptotic acinar cells by administration of antineutrophil serum, which, comparable to aICAM-1 (an intercellular adhesion molecule-1, neutralizing antibody), signifi cantly reduced the extent of necrosis and infl ammatory infi ltrate. Similar results were observed in another study wherein treatment with methotrexate resulted in a signifi cant depletion of neutrophils as shown by low myeloperoxidase levels and a consecutive increase in apoptotic acinar cell death [48] . Yet another study, using taurocholate-induced severe acute pancreatitis as the experimental model, showed that neutrophils, via a TNF-␣ -dependent mechanism, may be involved in the development of apoptotic as well as necrotic forms of acinar cell death [49] .…”

Acute experimental pancreatitis and NF-κB/rel activation

“…The involvement of apoptosis and necrosis in pancreatic acinar cells in rat models of experimental pancreatitis, such as pancreatic duct ligation, ethionine-induced pancreatitis, and cerulein-induced pancreatitis, has been shown by many investigators [27][28][29][30][31]. 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 [31].…”

“…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 [31]. Development of apoptosis may be negatively correlated with the severity of pancreatitis [31].…”

“…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 [31]. Development of apoptosis may be negatively correlated with the severity of pancreatitis [31]. Indeed NF-ÎB/Rel induces the expression of several genes that inhibit cell death by blocking different checkpoints of signaling pathways involved in the initiation of apoptosis [reviewed in 32].…”

Chemoprevention of biliary carcinogenesis in Syrian hamsters by the novel carboxamide derivative IS-741 after initiation with N -nitrosobis(2-oxopropyl)amine (BOP)

“…Am. than in non-cancerous regions of the liver, suggesting an In the present study, we determined the PLA 2 levels in non- damage (31,32). In the present study, neutrophils were noted cancer, but the role infiltrating inflammatory cells in biliary…”