INHIBITION OF SURFACTANT FUNCTION BY COPPER-ZINC SUPEROXIDE-DISMUTASE(CUZN-SOD)

The efficacy of antioxidant enzymes to Limit oxidant lung injury by in stillation with surfactant mixtures in preterm infants with hyaline me mbrane disease is under investigation. However, there is concern that instillation of proteins in the alveolar space may inactivate pulmonar y surfactant. We studied the effects of bovine copper-zinc superoxide dismutase (CuZn-SOD) on the biophysical properties of two distinct sur factant preparations. Incubation of calf lung surfactant extract (CLSE , 1 mg phospholipid/ml) and Exosurf (0.1 mg phospholipid/ml) with CuZn -SOD (1-10 mg/ml) prevented the fall of surface tension at minimal bub ble radius (T-min) to low values with dynamic compression in a pulsati ng bubble surfactometer. CuZn-SOD also enhanced the sensitivity to ina ctivation by albumin, normal human serum, and after treatment with per oxynitrite. The inhibitory effects of CuZn-SOD on CLSE, but not Exosur f, were abolished at high Lipid concentrations (3 mg/ml) and after the addition of human surfactant protein A (by weight). We conclude that CuZn-SOD may interfere with the surface activity of surfactant mixture s, leading to decreased effectiveness of surfactant replacement therap y.