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Modulation of glutaredoxin in the lung and sputum of cigarette smokers and chronic obstructive pulmonary disease

DOI: 10.1186/1465-9921-7-133

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Abstract:

Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD.Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I–II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051).The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung.The pathogenesis of chronic obstructive pulmonary disease (COPD) is probably strongly associated with reactive oxygen metabolites. Cigarette smoke not only contains high levels of oxidants, but it also leads to the accumulation of neutrophils and macrophages in the lung and to their activation [1-3]. A number of studies have investigated antioxidant defense mechanisms in cigarette smoke exposed cells and in chronic cigarette smokers. These studies have found that glutathione (GSH), a thiol containing tripeptide present in the epithelial lining fluid (ELF) at high concentrations, plays an essential role in protecting human airways against ex

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