Evidence for extracellular superoxide as a mediator of hemorrhage- induced lung injury

Hemorrhage results in excessive production of superoxide that is associated with severe lung injury. We examined whether the superoxide dismutase (SOD) mimetic manganese (III) meso-tetrakis (di-N-ethylimidazole) porphyrin (AEOL 10150) could attenuate this lung injury and whether extracellular SOD (EC-SOD) deficient mice would have increased hemorrhageinduced lung injury. Compared to wildtype mice, EC-SOD deficient mice had increased lung neutrophil accumulation, a 3.9-fold increase in myeloperoxidase activity, a 1.5-fold increase in nuclear factor-k B activation and a 1.5-fold increase in lipid peroxidation one hour after hemorrhage. Pretreatment with AEOL 10150 did not attenuate neutrophil accumulation, but significantly reduced NF-kB activation and lipid peroxidation in both wildtype and EC-SOD deficient mice. The increase in hemorrhage-induced neutrophil accumulation in the lungs of ECSOD deficient mice suggest that EC-SOD might play a role in mediating neutrophil recruitment to the lung.