Oxidative damage to nucleic acids in severe 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 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.
Deslee
Gaetan
G
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Woods
Jason C
JC
Department of Radiology, Washington University School of Medicine, St. Louis, MO.
Moore
Carla
C
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Conradi
Susan H
SH
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Gierada
David S
DS
Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
Atkinson
Jeffrey J
JJ
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Battaile
John T
JT
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Liu
Lucy
L
Department of Physics, Washington University School of Medicine, St. Louis, MO.
Patterson
G Alexander
GA
Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO.
Adair-Kirk
Tracy L
TL
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Holtzman
Michael J
MJ
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO.
Pierce
Richard A
RA
Division of Pulmonary and Critical Care Medicine, Washington University School of Medicine, St. Louis, MO. Electronic address: rpierce@im.wustl.edu.
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007120:Immunochemistry; D019272:Leukocyte Elastase / Q000032:analysis; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology; D011656:Pulmonary Emphysema / Q000378:metabolism*; D012313:RNA / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D004247:DNA; D019272:Leukocyte Elastase; D009696:Nucleic Acids; D012313:RNA; C067980:CD68 antigen, human; D000097382:CD68 Molecule