Inhibition of surfactant function by copper-zinc superoxide dismutase (CuZn-SOD)

The efficacy of antioxidant enzymes to limit oxidant lung injury by instillation with surfactant mixtures in preterm infants with hyaline membrane disease is under investigation. However, there is concern that instillation of proteins in the alveolar space may inactivate pulmonary surfactant. We studied the effects of bovine copper-zinc superoxide dismutase (CuZn-SOD) on the biophysical properties of two distinct surfactant 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 bubble radius (Tmin) to low values with dynamic compression in a pulsating bubble surfactometer. CuZn-SOD also enhanced the sensitivity to inactivation by albumin, normal human serum, and after treatment with peroxynitrite. The inhibitory effects of CuZn-SOD on CLSE, but not Exosurf, 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 mixtures, leading to decreased effectiveness of surfactant replacement therapy.