Decreased haem oxygenase-1 and increased inducible nitric oxide synthase in the lung of severe COPD patients.

Oxidant/antioxidant imbalance is implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The current study examined the expression of antioxidant and pro-oxidant enzymes, haem oxygenases (HO) and inducible nitric oxide synthase (iNOS) respectively, in patients with severe COPD and control smokers without lung function impairment. Immunoreactivity for HO-1, HO-2, iNOS and nitric oxide-derived oxidants expressed as nitrotyrosine (N-Tyr) was quantified in peripheral lung. HO-1+ alveolar macrophages were decreased in severe COPD compared to control smokers, whereas no difference was observed in iNOS+ macrophages. In contrast, severe patients had significantly higher numbers of iNOS+ cells in alveolar walls. These iNOS+ cells were identified as type 2 pneumocytes and their number was inversely related to HO-1+ macrophages. There were no significant differences in N-Tyr immunostaining between the two groups. However, the rate of protein nitration in lung tissue was directly related to iNOS expression and associated with lower values of forced expiratory volume in one second/forced vital capacity. HO-2 was constitutively expressed by type 2 pneumocytes and these cells were increased in severe COPD. In conclusion, the results suggest that the enzymes involved in the oxidative stress response may have a different role in the lung defence and that imbalance between haem oxygenase-1 and inducible nitric oxide synthase may be associated with the development of severe impairment in chronic obstructive pulmonary disease patients.

Increased expression of heme oxygenase (HO)-1 in alveolar spaces and HO-2 in alveolar walls of smokers.

It has been suggested that oxidative stress protein heme oxygenase (HO)-1 plays a role in chronic airway diseases including chronic obstructive pulmonary disease (COPD). The inducible isoform HO-1 and the constitutive HO-2 catalyze the same reaction. Their distribution in situ was studied in lungs of 10 nonsmoking subjects, 6 healthy smokers, and 10 smokers with COPD. Paraffin-embedded sections of surgical lung specimens were immunostained with antibodies against HO-1 and HO-2. HO-1 immunoreactivity was observed mainly in alveolar macrophages. HO-1-positive macrophages were increased in smokers with COPD (median: 36%) as compared with nonsmoking subjects (13%; p < 0.02), whereas no differences were observed between patients with COPD and healthy smokers (34%). HO-2 had a more widespread distribution in cells of the alveolar wall, in adventitia of pulmonary arteries and bronchioles, and in vascular smooth muscle. Lower percentages of alveolar macrophages exhibited positive staining for HO-2 without significant differences between the three groups. HO-2(+) cells in the alveolar wall were increased in smokers with (15/mm) and without COPD (12/mm) as compared with nonsmokers (8/mm, p < 0.01). In conclusion, inducible HO-1 and constitutive HO-2 are detectable in human lung tissue and their expression is increased in smokers, suggesting that oxidative stress due to cigarette smoke may increase lung cells expressing HO-1 and HO-2.