Research

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

Mirva J Peltoniemi^1,2 , Paula H Rytilä³ , Terttu H Harju² , Ylermi M Soini⁴ , Kaisa M Salmenkivi⁵ , Lloyd W Ruddock¹ and Vuokko L Kinnula⁶

¹  Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland

²  Department of Internal Medicine, University of Oulu, Oulu, Finland

³  Department of Medicine, Division of Allergology, University of Helsinki, Helsinki, Finland

⁴  Department of Pathology, Oulu University Hospital, Oulu, Finland

⁵  Department of Pathology, Helsinki University Hospital, Helsinki, Finland

⁶  Biomedicum Helsinki and Department of Medicine, Division of Pulmonary Diseases, PO Box 340 (Haartmaninkatu 4), 00029 Helsinki University Hospital, Helsinki, Finland

author email corresponding author email

Respiratory Research 2006, 7:133doi:10.1186/1465-9921-7-133

Published:	25 October 2006

Abstract

Background

One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear.

Methods

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.

Results

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).

Conclusion

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.