Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2 R. DUNCAN HITE,1 MICHAEL C. SEEDS,1 RANDY B. JACINTO,1 R. BALASUBRAMANIAN,1 MOSELEY WAITE,2 AND DAVID BASS1

Hite, R. Duncan, Michael C. Seeds, Randy B. Jacinto, R. Balasubramanian, Moseley Waite, and David Bass. Hydrolysis of surfactant-associated phosphatidylcholine by mammalian secretory phospholipases A2. Am. J. Physiol. 275 (Lung Cell. Mol. Physiol. 19): L740–L747, 1998.—Hydrolysis of surfactant-associated phospholipids by secretory phospholipases A2 is an important potential mechanism for surfactant dysfunction in inflammatory lung diseases. In these conditions, airway secretory phospholipase A2 (sPLA2) activity is increased, but the type of sPLA2 and its impact on surfactant function are not well understood. We examined in vitro the effect of multiple secretory phospholipases A2 on surfactant, including their ability to 1) release free fatty acids, 2) release lysophospholipids, and 3) increase the minimum surface tension (gmin) 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 A2. Our results demonstrate that mammalian group I sPLA2 hydrolyzes phosphatidylcholine (PC), producing free fatty acids and lysophosphatidylcholine, and increases gmin. In contrast, mammalian group II sPLA2 demonstrates limited hydrolysis of PC and does not increase gmin. Group I and group II secretory phospholipases A2 from snake venom hydrolyze PC and inhibit surfactant function. In summary, mammalian secretory phospholipases A2 from groups I and II differ significantly from each other and from snake venom in their ability to hydrolyze surfactant-associated PC.