Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2

Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A(2) is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A(2) (sPLA(2)) activity is increased, but the type of sPLA(2) and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A(2) on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (gamma(min)) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (recombinant porcine pancreatic) and group II (recombinant human) secretory phospholipases A(2). Our results demonstrate that mammalian group I sPLA(2) hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases gamma(min). In contrast, mammalian group II sPLA(2) demonstrates Limited hydrolysis of PC and does not increase gamma(min). Group I and group II secretory phospholipases A(2) from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A(2) from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.