Pivotal role of anionic phospholipids in determining dynamic behavior of lung surfactant.

Abstract

Phosphatidylglycerol (PG) and phosphatidylinositol (PI) are anionic phospholipids (APLs) present in lung surfactant of virtually all species studied, although their specific contribution to function is unknown. This study examines how APLs influence surfactant monolayer stability and adsorption under static and dynamic conditions. Interfacial properties of surfactants reconstituted with native phospholipids (PL), and phospholipids devoid of anionic species (DAPL), were characterized by pulsating bubble surfactometry. Measurements were made for PL and DAPL alone; with 3% surfactant proteins B and C (SP-B/C); with SP-B/C and 5% surfactant protein A (SP-A); and with SP-B/C, SP-A, and 8% neutral lipids (NL). Equilibrium and dynamic properties of PL and DAPL were similar. However, whereas (DAPL + SP-B/C) and (DAPL + SP-B/C + SP-A) mixtures were similar to corresponding PL mixtures with respect to gamma(equil), they displayed markedly different dynamic behavior. In particular, the degree of film compression required to reach gamma(min) was significantly increased in DAPL mixtures (80 to 90% area reduction) compared with PL, although both samples reached gamma(min) < 3.0 dynes/cm. The addition of NL to (DAPL + SP-B/C + SP-A) produced an increase in gamma(min) to 15 to 20 dynes/cm during dynamic compression, whereas NL had no significant impact on the behavior of (PL + SP-B/C + SP-A). Purified PG (5% wt/wt) restored nearly normal dynamic properties to (DAPL + SP-B/C + SP-A + NL), whereas phosphatidylcholine (PC) (5% wt/wt) had no beneficial effect. These results suggest that APLs play a critical role in promoting surface film stability during dynamic compression through interactions with nonlipid surfactant components, and prevent destabilization of the surface film by cholesterol and other NL.