Journal
CHEST
Volume 135, Issue 4, Pages 965-974Publisher
ELSEVIER SCIENCE BV
DOI: 10.1378/chest.08-2257
Keywords
alpha(1)-antitrypsin deficiency; emphysema; nucleic acids; oxidative stress; RNA
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Funding
- National Institutes of Health [P50HL084922]
- Region Champagne-Ardenne
- University and CHU of Reims
- ARAIRCHAR
- College des Professeurs de Pneumologie and AstraZeneca
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Background: Oxidative stress is a key element in the pathogenesis of emphysema, but oxidation of nucleic acids has been largely overlooked. The aim of this study was to investigate oxidative damage to nucleic acids in severe emphysematous lungs. Methods: Thirteen human severe emphysematous lungs, including five with alpha(1)-antitrypsin deficiency (AATD), were obtained from patients receiving lung transplantation. Control lung tissue was obtained from non-COPD lungs (n = 8) and donor lungs (n = 8). DNA kind RNA oxidation were investigated by immunochemistry. Morphometry (mean linear intercept [Lm] and CT scan) and immunostaining for CD68 and neutrophil elastase also were performed. Results: Nucleic acid oxidation was increased in alveolar wall cells. in emphysematous lungs compared to non-COPD and donor lungs (p < 0.01). In emphysematous lungs, oxidative damage to nucleic acids in alveolar wall cells was increased in the more severe emphysematous areas assessed by histology (Lm, > 0.5 mm; p < 0.05) and CT scan (< -950 Hounsfield units; p < 0.05). Compared to classic emphysema, AATD lungs exhibited higher levels of nucleic acid oxidation in macrophages (p < 0.05) and airway epithelial cells (p < 0.01). Pretreatments with DNase and RNase demonstrated that RNA oxidation was more prevalent than DNA oxidation in alveolar wall cells. Conclusions: We demonstrated for the first time that nucleic acids, especially, RNA, are oxidized in human emphysematous lungs. The correlation between the levels of oxidative damage to nucleic acids in alveolar wall cells and the severity of emphysema suggest a potential role in the pathogenesis of emphysema.
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