Gaetan Deslee1, Jason C Woods2, Carla Moore1, Susan H Conradi3, David S Gierada3, Jeffrey J Atkinson1, John T Battaile1, Lucy Liu4, G Alexander Patterson5, Tracy L Adair-Kirk1, Michael J Holtzman1, Richard A Pierce6. 1. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO. 2. Department of Radiology, Washington University School of Medicine, St. Louis, MO. 3. Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO. 4. Department of Physics, Washington University School of Medicine, St. Louis, MO. 5. Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO. 6. Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO. Electronic address: rpierce@im.wustl.edu.
Abstract
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 and 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.
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 and 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 humanemphysematous 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.
Authors: Jason C Woods; Cliff K Choong; Dmitriy A Yablonskiy; John Bentley; Jonathan Wong; John A Pierce; Joel D Cooper; Peter T Macklem; Mark S Conradi; James C Hogg Journal: Magn Reson Med Date: 2006-12 Impact factor: 4.668
Authors: Gaetan Deslee; Tracy L Adair-Kirk; Tomoko Betsuyaku; Jason C Woods; Carla H Moore; David S Gierada; Susan H Conradi; Jeffrey J Atkinson; Holly M Toennies; John T Battaile; Dale K Kobayashi; G Alexander Patterson; Michael J Holtzman; Richard A Pierce Journal: Am J Respir Cell Mol Biol Date: 2009-12-11 Impact factor: 6.914
Authors: Catherine R Sears; Huaxin Zhou; Matthew J Justice; Amanda J Fisher; Jacob Saliba; Isaac Lamb; Jessica Wicker; Kelly S Schweitzer; Irina Petrache Journal: Am J Respir Cell Mol Biol Date: 2018-03 Impact factor: 6.914