The generation of lysolecithin by enterokinase in trypsinogen prophospholipase A 2 lecithin mixtures, and its relevance to the pathogenesis of acute necrotising pancreatitis

Abstract

The cascade enterokinase-trypsinogen-prophospholipase A 2 lecithin, generating trypsin, phospholipase A 2 and lysolecithin, respectively, was studied in vitro using a novel phospholipase A 2 assay. The rate of enterokinase catalysed activation of trypsinogen was maximal at 4 mmol/l glycodeoxycholic acid; higher concentrations of bile salt progressively inhibited enterokinase activity. Net phospholipase A 2 activity in reaction mixtures was critically dependent on the trypsin/prophospholipase A 2 molar ratio. Lecithin hydrolysis by phospholipase A 2 was dependent on the bile salt/lecithin molar ratio and was optimal at 1.25 to 1. The addition of enterokinase to lecithin and bile salt mixtures, containing trypsinogen and prophospholipase A 2 at presumed pathophysiological concentrations, resulted in the generation of concentrations of lysolecithin lytic for pancreatic acinar cells within 5 min. These findings would support the concept that the entry of bile containing active enterokinase into the pancreatic duct system in vivo may in some cases be involved in the initiation of necrotising acute pancreatitis in man.