Phospholipase A2 isoforms in acute pancreatitis

Objective To assess phospholipase A2 isoforms during human and experimental acute necrotizing pancreatitis. Phospholipase A2 isoforms (group I, Ii, an d IV) were examined in acute pancreatitis tissues in humans and rats to det ermine whether the exocrine pancreas itself is a source of these mediators. Summary Background Data Phospholipase A2 has important regulatory functions , especially in inflammation. Methods Using Northern blot analysis and immunohistochemistry, the expressi on and localization of phospholipase A2 isoforms were analyzed in pancreati c tissue obtained from 21 patients with acute necrotizing pancreatitis and in pancreatic tissues of rats with acute edematous and necrotizing pancreat itis. Rat samples were examined daily for 1 week. Results In human acute pancreatitis, phospholipase A2-I mRNA expression was 8.9-fold decreased. By contrast, phospholipase A2-II (7.8-fold) and phosph olipase A2-IV (8.1-fold) mRNA levels were increased. By in situ hybridizati on, phospholipase A2-IV was found to be expressed in remaining acinar and d uctal cells adjacent to the necrotic areas. Immunostaining revealed moderat e to intense phospholipase A2-II immunoreactivity in remaining acinar and d uctal cells next to the necrosis. In rat pancreatitis, phospholipase A2-II mRNA levels in the pancreas were unchanged in the early phase (8 hours) but markedly increased after 24 hours, with a fluctuating pattern until day 7. Conclusions Enhanced expression of phospholipase A2-II and A2-IV isoenzymes in human and experimental acute pancreatitis suggests that these enzymes p lay a role in modulating the inflammatory reaction in the pancreas. Because phospholipase A2-II and A2-IV mRNA was strongly present in remaining viabl e pancreatic acinar and ductal cells, the pancreas itself seems to be at le ast partly a source and a regulator of phospholipase A2-II and A2-IV-depend ent inflammatory reactions in acute pancreatitis.