HYDROLYSIS OF SURFACTANT-ASSOCIATED PHOSPHATIDYLCHOLINE BY MAMMALIAN SECRETORY PHOSPHOLIPASES A(2)

Hydrolysis of surfactant-associated phospholipids by secretory phospho lipases A(2) is an important potential mechanism for surfactant dysfun ction in inflammatory lung diseases. In these conditions, airway secre tory phospholipase A(2) (sPLA(2)) activity is increased, but the type of sPLA(2) and its impact on surfactant function are not well understo od. We examined in vitro the effect of multiple secretory phospholipas es A(2) on surfactant, including their ability to 1) release free fatt y acids, 2) release lysophospholipids, and 3) increase the minimum sur face tension (gamma(min)) on a pulsating bubble surfactometer. Natural porcine surfactant and Survanta were exposed to mammalian group I (re combinant porcine pancreatic) and group II (recombinant human) secreto ry phospholipases A(2). Our results demonstrate that mammalian group I sPLA(2) hydrolyzes phosphatidylcholine (PC), producing free fatty aci ds 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 phospholi pases A(2) from snake venom hydrolyze PC and inhibit surfactant functi on. In summary, mammalian secretory phospholipases A(2) from groups I and II differ significantly from each other and from snake venom in th eir ability to hydrolyze surfactant-associated PC.