Characterization of the acute pancreatitis induced by secretory phospholipases A 2 in rats

Abstract

Acute pancreatitis (AP) is an inflammatory disease of the pancreas characterized by local inflammation and extrapancreatic effects such as lung injury. Secretory phospholipases A 2 (PLA 2s) have been implicated in triggering AP, but their exact role to evoke AP is largely unknown. Therefore, we have tested the ability of sPLA 2s to induce AP in rats, using venom sPLA 2s with residual or high enzymatic activity (bothropstoxin-II and Naja mocambique mocambique venom PLA 2, respectively), as well as sPLA 2 devoid of catalytic activity (piratoxin-I). The injection of Naja m. mocambique venom PLA 2, bothropstoxin-II or piratoxin-I (300 μg/kg each) into the common bile duct increased significantly the pancreatic plasma extravasation and myeloperoxidase activity. The lung myeloperoxidase and serum amylase were also increased for all groups, although the Naja mocambique mocambique venom PLA 2 induced higher lung myeloperoxidase and serum amylase values, compared with piratoxin-I and/or bothropstoxin-II. Histopathology of pancreas and lungs in piratoxin-I-injected rats showed interstitial oedema in both tissues, and neutrophil infiltration with acinar cell necrosis in pancreas. In conclusion, sPLA 2s induce AP in rats and the catalytic activity is not essential to induce the local effects in pancreas, although it appears to contribute partly to the remote lung injury.