Specific interaction of pancreatic elastase and leukocytes to produce oxygen radicals and its implication in pancreatitis

点击翻译按钮获取中文摘要

Many previous reports using experimental animal models of pancreatitis have suggested that oxygen free radicals plays an important role in initiation and development of pancreatitis. Infiltration of inflammatory cells, i.e., neutrophils, lymphocytes and monocytes, has been observed in damaged pancreatic glands of animal models and patients of pancreatitis. Neutrophils are known to be the highest producer of oxygen free radicals among these inflammatory cells, it seems plausible that oxygen free radicals produced by neutrophils have some pathoetiological meaning in pancreatitis. In the present study we measured the superoxide production by nutrophils obtained from patients with acute and chronic pancreatitis, and then examined the effects of pancreatic enzymes on superoxide production. Patients showed significantly higher superoxide production by 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA)-stimulated neutrophils than healthy controls did. Among the three pancrestic enzymes, amylase, trypsin and elastase, elastase was the only one which increased the superoxide production by PMA-stimulated neutrophils, by an increment of 1.5-fold. It also increased the activity of NADPH oxidase prepared from PMA-stimulated neutrophils by a factor of 2.1. High affinity and low affinity binding sites fot elastase on neutrophils were identified. These results suggest that elastase plays a role in the development of pancreatitis by enhancing superoxide production of neutrophils.