Am. J. Respir. Crit. Care Med., Volume 164, Number 2, July 2001, 290-294

Extracellular Superoxide Dismutase Attenuates Lung Injury after Hemorrhage

RUSSELL P. BOWLER, JOHN ARCAROLI, JAMES D. CRAPO, ARON ROSS, JAN W. SLOT, and EDWARD ABRAHAM

National Jewish Medical and Research Center, Denver, Colorado; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado; and Department of Pathology, University of Utrecht, Utrecht, The Netherlands

Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O₂^·) that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 ± 0.11 in unmanipulated 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 wild-type). Hemorrhage-induced lipid peroxidation, as assessed by lung F₂ isoprostanes, was lower in the EC-SOD transgenic mice (3.4 ± 0.3 µg/lung) compared with wild-type mice (1.9 ± 0.2 µg/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK-B) activation (relative absorbance 1.1 ± 0.2 for EC-SOD transgenic versus 2.5 ± 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 ± 0.87 units/g for EC-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 injury after hemorrhage.

Keywords: hemorrhage; extracellular superoxide dismutase; NF-B; myeloperoxidase

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