Extracellular superoxide dismutase attenuates lung injury after hemorrhage

Reperfusion of the lung after hemorrhage generates free radicals such as su peroxide (O-2') that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superox ide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxi de dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wildt ype mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhag e, the lung wet to dry weight ratios increased from 5.4 +/- 0.11 in unmanip ulated control mice to 6.3 +/- 0.16 in wild-type mice, but to only 5.60 +/- 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wil dtype). Hemorrhage-induced lipid peroxidation, as assessed by lung F-2 isop rostanes, was lower in the EC-SOD transgenic mice (3.4 +/- 0.3 mug/lung) co mpared with wild-type mice (1.9 +/- 0.2 mug/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced inc rease in both pulmonary nuclear factor kappa B (NK-kappaB) activation (rela tive absorbance 1.1 +/- 0.2 for EC-SOD transgenic versus 2.5 +/- 0.1 for wi ld-type; p < 0.05) and myeloperoxidase activity (5.1 +/- 0.87 units/g for E C-SOD transgenic versus 11.3 +/- 1.8 units/g for wild-type; p < 0.01). Thus , overexpression of pulmonary EC-SOD in the mouse lung attenuates lung inju ry after hemorrhage.