Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients.

Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited. p53 and bcl2 protein expression was measured by western blot on lung tissue specimens from 43 subjects (23 COPD smokers and 20 non-COPD smokers), using beta-actin as internal control. Additionally, p53 and bcl2 expression patterns were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same individuals. Western blot analysis showed statistically significant increased p53 protein levels in COPD smokers in comparison with non-COPD smokers (p = 0.038), while bcl2 protein levels were not statistically different between the two groups. Lung immunohistochemistry showed increased ratio of positive p53-stained type II pneumocytes/total type II pneumocytes in COPD smokers compared to non-COPD smokers (p = 0.01), whereas the p53 staining ratio in alveolar macrophages and in lymphocyte-like cells did not differ statistically between the two groups. On the other hand, bcl2 expression did not differ between the two groups in all three cell types. The increased expression of pro-apoptotic p53 in type II pneumocytes of COPD patients not counterbalanced by the anti-apoptotic bcl2 could reflect increased apoptosis in the alveolar epithelium of COPD patients. Our results confirm previous experiments and support the hypothesis of a disturbance in the balance between the pro- and anti-apoptotic mediators in COPD.

Altered surfactant protein-A expression in type II pneumocytes in COPD.

BACKGROUND: Pulmonary surfactant protein A (SP-A) is a lectin, with multiple functions that contribute to innate host defense and the regulation of the inflammatory process in the lung. In normal conditions, SP-A seems to protect against the effects of smoking. However, studies in smokers with or without COPD are limited. METHODS: Western blots on lung tissue specimens from 60 male subjects (32 patients with COPD, 18 smokers without COPD, and 10 control nonsmokers) for SP-A and the housekeeping protein actin were carried out. Additionally, the SP-A expression pattern was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded lung tissue sections from the same subjects. RESULTS: Western blots revealed significantly higher SP-A levels in control nonsmokers (4.8 +/- 0.05) when compared with patients with COPD (0.6 +/- 0.7) and smokers without COPD (2.4 +/- 0.9), (P < .05). However, differences that were not statistically significant were observed in SP-A levels among the patients with COPD and the smokers without COPD (P = .12). The immunohistochemical examinations showed an increase in the overall number of type II pneumocytes per high-power field in patients with COPD, but a decreased ratio of SP-A positive type II pneumocytes to total type II pneumocytes, compared with smokers without COPD (P = .001). This ratio was also correlated with FEV(1) (percent predicted [% pred]), (r = 0.490, P = .001). The overall number of alveolar macrophages per high-power field was significantly higher in patients with COPD compared with smokers without COPD (P = .001). The ratio of SP-A positive alveolar macrophages was increased in patients with COPD when compared with smokers without COPD (P = .002), while this was correlated with airway obstruction (FEV(1), % pred) (r = 0.281, P = .04). CONCLUSIONS: Our results indicate that altered SP-A expression could be another link to COPD pathogenesis and highlights the need for further studies on surfactant markers in COPD.