title: Smoking and COPD increase sputum levels of extracellular superoxide dismutase.
abstract: Extracellular superoxide dismutase (ECSOD) is the major superoxide-scavenging enzyme in the lung. Certain ECSOD polymorphisms are protective against COPD. We postulated that smokers and COPD subjects would have altered levels of ECSOD in the lung, airway secretions, and/or plasma. Lung tissue ECSOD was evaluated from nonsmokers, smokers, and subjects with mild to very severe COPD by Western blot, immunohistochemistry, and ELISA. ECSOD levels in plasma, bronchoalveolar lavage fluid (BALF), and induced-sputum supernatants were analyzed by ELISA and correlated with smoking history and disease status. Immunohistochemistry identified ECSOD in extracellular matrix around bronchioles, arteries, and alveolar walls, with decreases seen in the interstitium and vessels of severe COPD subjects using digital image analysis. Plasma ECSOD did not differ between COPD subjects and controls nor based on smoking status. ECSOD levels in induced sputum supernatants were elevated in current smokers and especially in COPD subjects compared to nonsmokers, whereas corresponding changes could not be seen in the BALF. ECSOD expression was reduced around vessels and bronchioles in COPD lungs. Substantial increases in sputum ECSOD in smokers and COPD is interpreted as an adaptive response to increased oxidative stress and may be a useful biomarker of disease activity in COPD.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA. regane@NJhealth.org
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Regan
authors.forename: Witold
authors.initials: W
authors.lastname: Mazur
authors.forename: Eleonora
authors.initials: E
authors.lastname: Meoni
authors.forename: Tuula
authors.initials: T
authors.lastname: Toljamo
authors.forename: Julie
authors.initials: J
authors.lastname: Millar
authors.forename: Katri
authors.initials: K
authors.lastname: Vuopala
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Irfan
authors.initials: I
authors.lastname: Rahman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Nicks
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.forename: Vuokko L
authors.initials: VL
authors.lastname: Kinnula
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010949:Plasma / Q000737:chemistry; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000201:enzymology* / Q000503:physiopathology; D012907:Smoking / Q000009:adverse effects; D013183:Sputum / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000276:immunology / Q000378:metabolism*
chemical_list: C441642:SOD3 protein, human; D013482:Superoxide Dismutase