Surface properties of sulfur- and ether-linked phosphonolipids with and without purified hydrophobic lung surfactant proteins

Two novel C16:0 sulfur-linked phosphonolipids (S-lipid and SO2-lipid) and two ether-linked phosphonolipids (C16:0 DEPN-8 and C16:1 UnDEPN-8) were studied for surface behavior alone and in mixtures with purified bovine lung surfactant proteins (SP)-B and/or SP-C. Synthetic C16:0 phosphonolipids all had improved adsorption and film respreading compared to dipalmitoyl phosphatidylcholine, and SO2-lipid and DEPN-8 reached maximum surface pressures of 72 mN/m (minimum surface tensions of <1 mN/m) in compressed films on the Wilhelmy balance (23 °C). Dispersions of DEPN-8 (0.5 mg/ml) and SO2-lipid (2.5 mg/ml) also reached minimum surface tensions of <1 mN/m on a pulsating bubble surfactometer (37 °C, 20 cycles/min, 50% area compression). Synthetic lung surfactants containing DEPN-8 or SO2-lipid + 0.75% SP-B + 0.75% SP-C had dynamic surface activity on the bubble equal to that of calf lung surfactant extract (CLSE). Surfactants containing DEPN-8 or SO2-lipid plus 1.5% SP-B also had very high surface activity, but less than when both apoproteins were present together. Adding 10 wt.% of UnDEPN-8 to synthetic lung surfactants did not improve dynamic surface activity. Surfactants containing DEPN-8 or SO2-lipid plus 0.75% SP-B/0.75% SP-C were chemically and biophysically resistant to phospholipase A2 (PLA2), while CLSE was severely inhibited by PLA2. The high activity and inhibition resistance of synthetic surfactants containing DEPN-8 or SO2-lipid plus SP-B/SP-C are promising for future applications in treating surfactant dysfunction in inflammatory lung injury.