Glutathione-S-transferases in lung and sputum specimens, effects of smoking and COPD severity.
BACKGROUND
Oxidative stress plays a potential role in the pathogenesis and progression of chronic obstructive pulmonary disease (COPD). Glutathione S-transferases (GSTs) detoxify toxic compounds in tobacco smoke via glutathione-dependent mechanisms. Little is known about the regulation and expression of GSTs in COPD lung and their presence in airway secretions.


METHODS
GST alpha, pi and mu were investigated by immunohistochemistry in 72 lung tissue specimens and by Western analysis in total lung homogenates and induced sputum supernatants from non-smokers, smokers and patients with variable stages of COPD severity.


RESULTS
GST alpha was expressed mainly in the airway epithelium. The percentage of GST alpha positive epithelial cells was lower in the central airways of patients with very severe (Stage IV) COPD compared to mild/moderate COPD (p = 0.02). GST alpha by Western analysis was higher in the total lung homogenates in mild/moderate COPD compared to cases of very severe disease (p < 0.001). GST pi was present in airway and alveolar epithelium as well as in alveolar macrophages. GST mu was expressed mainly in the epithelium. Both GST alpha and pi were detectable in sputum supernatants especially in patients with COPD.


CONCLUSIONS
This study indicates the presence of GST alpha and pi especially in the epithelium and sputum supernatants in mild/moderate COPD and low expression of GST alpha in the epithelium in cases of very severe COPD. The presence of GSTs in the airway secretions points to their potential protective role both as intracellular and extracellular mediators in human lung.
Harju
Terttu
T
Institute of Clinical Medicine, Department of Internal Medicine, Centre of Excellence in Research, P O Box 5000, 90014 University of Oulu, Oulu, Finland. terttu.harju@oulu.fi
Mazur
Witold
W
Merikallio
Heta
H
Soini
Ylermi
Y
Kinnula
Vuokko L
VL
D000368:Aged; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000201:enzymology*; D012720:Severity of Illness Index; D012907:Smoking / Q000378:metabolism*; D013183:Sputum / Q000201:enzymology*
D005982:Glutathione Transferase