Extracellular superoxide dismutase protects against pulmonary emphysema by attenuating oxidative fragmentation of ECM

• DOI: 10.1073/pnas.1007625107
• Publication Date: 2010-08-17T04:40:39Z
• Authors: Hongwei Yao; Gnanapragasam Aru...; Jae-woong Hwang; Sangwoon Chung; Isaac K. Sundar; Vuokko L. Kinnula; James D. Crapo; Irfan Rahman
• Keywords: Mice, Knockout; 0303 health sciences; Pancreatic Elastase; Metalloporphyrins; Neutrophils; Superoxide Dismutase; Swine; Immunoblotting; Mice, Transgenic; Elastin; Extracellular Matrix; 3. Good health; Mice, Inbred C57BL; Mice; Oxidative Stress; 03 medical and health sciences; Pulmonary Emphysema; Smoke; Animals; Heparitin Sulfate; Bronchoalveolar Lavage Fluid; Lung; Lung Compliance

Extracellular superoxide dismutase (ECSOD or SOD3) is highly expressed in lungs and functions as a scavenger of O(2)(*-). ECM fragmentation, which can be triggered by oxidative stress, participates the pathogenesis chronic obstructive pulmonary disease (COPD) through attracting inflammatory cells into lungs. The level SOD3 significantly decreased patients with COPD. However, role endogenous development/progression emphysema unknown. We hypothesized that protects against attenuating fragmentation mice. To test this hypothesis, SOD3-deficient, SOD3-transgenic, WT C57BL/6J mice were exposed to cigarette smoke (CS) for 3 d (300 mg total particulate matter/m(3)) 6 mo (100 mg/m(3) matter) intratracheal elastase injection. Airspace enlargement, lung inflammation, mechanical properties, exercise tolerance determined at different time points during CS exposure after administration. administration caused airspace enlargement well impaired function capacity SOD3-null mice, improved overexpressing pharmacological SOD mimetic. These phenomena associated SOD3-mediated protection ECM, such heparin sulfate elastin, thereby response. In conclusion, attenuates reduces mouse lung. Thus, augmentation may have therapeutic potential intervention COPD/emphysema.