EXPOSURE OF THE HYDROPHOBIC COMPONENTS OF PORCINE LUNG SURFACTANT TO OXIDANT STRESS ALTERS SURFACE-TENSION PROPERTIES

We have tested the hypothesis that oxidation of lung surfactant result s in loss of surface tension lowering function. Porcine lung surfactan t was exposed to conditions known to cause Lipid peroxidation (0.2 nM FeCl2 + 0.1 mM H2O2 or 5 mu M CuCl2). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substa nces, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tens ion lowering ability in vitro as measured in a bubble surfactometer. S amples exposed to FeCl2 + H2O2 had significantly diminished surface te nsion lowering ability in vivo as indicated by their reduced ability t o improve lung compliance of surfactant-deficient fetal rabbits. Oxida tion of phospholipid mixtures with surface tension lowering activity a nd containing unsaturated acyl groups resulted in partial loss of acti vity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on th e phospholipid components and that acute pulmonary inflammation accomp anied by oxygen radical production may result in surfactant lipid pero xidation and loss of surface tension lowering function.