Effects of exogenous surfactant and recombinant human copper-zinc superoxide dismutase on oxygen-dependent antimicrobial defenses

The use of human recombinant CuZn superoxide dismutase (rhSOD) in addition to exogenous surfactant has been studied as a therapeutic strategy to prevent acute and chronic lung injury in premature infants with blood monocytes (MO). However, scavenging of superoxide by rhSOD may compromise bacterial killing by phagocytes. In the present study, we investigated the interaction of exogenous surfactant and rhSOD with the antibacterial activity of human blood MO. MO were preincubated in the presence or absence of: (1) modified natural surfactant (Curosurf®; 1 mg/ml); (2) rhSOD (2,500 U/ml) and (3) bovine catalase (25,000 U/ml). Bacteria (Legionella pneumophila or Escherichia coli) were then added and incubated for 6 h. Viable bacteria were determined by counting colony-forming units. The ability of the MO to generate superoxide anions (O–2) in response to bacterial infection was also investigated. The antibacterial capacity of MO was not impaired by the presence of rhSOD either alone or combined with Curosurf®. In some instances, bactericidal activity was even potentiated by the addition of rhSOD. Exposure of MO to catalase interfered with the increased bacterial killing of MO and rhSOD, suggesting that hydrogen peroxide (H2O2) production was critically important in the process of bacterial killing. Both bacterial species were also found to induce the generation of intra- and extracellular O–2 by MO. Data indicate that rhSOD potentiates the killing of bacteria by human MO. The mechanism of action appears to be related to the ability of bacteria to induce the generation of O–2, which in turn is converted to H2O2 in the presence of rhSOD. This has important implications in the development of therapeutic intervention strategies using antioxidant therapy in premature infants with respiratory distress syndrome.