0
Original Research: COPD |

Oxidative Damage to Nucleic Acids in Severe Emphysema

Gaetan Deslee, MD; Jason C. Woods, PhD; Carla Moore; Susan H. Conradi, PhD; David S. Gierada, MD; Jeffrey J. Atkinson, MD; John T. Battaile, MD; Lucy Liu; G. Alexander Patterson, MD, FCCP; Tracy L. Adair-Kirk, PhD; Michael J. Holtzman, MD; Richard A. Pierce, PhD
Author and Funding Information

*From the Division of Pulmonary and Critical Care Medicine (Drs. Deslee, Atkinson, Battaile, Adair-Kirk, Holtzman, and Pierce, and Ms. Moore), the Departments of Radiology (Dr. Woods) and Physics (Ms. Liu), the Mallinckrodt Institute of Radiology (Drs. Conradi and Gierada), and the Division of Cardiothoracic Surgery (Dr. Patterson), Washington University School of Medicine, St. Louis, MO.

Correspondence to: Richard A. Pierce, PhD, Washington University School of Medicine, Division of Pulmonary and Critical Care Medicine, Campus Box 8052, 660 South Euclid Ave, St. Louis, MO 63110; e-mail: rpierce@im.wustl.edu


This study was supported by National Institutes of Health grant P50HL084922. Dr. Deslee received grants for postdoctoral training from Region Champagne-Ardenne, University and CHU of Reims, ARAIRCHAR, College des Professeurs de Pneumologie and AstraZeneca.

No conflict of interest exists for any of the authors.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(4):965-974. doi:10.1378/chest.08-2257
Text Size: A A A
Published online

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 α1-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.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543