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Imbalance of Apoptosis and Cell Proliferation Contributes to the Development and Persistence of Emphysema

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Abstract

Background

We postulate that in adults there is an established lung structure maintenance program and that lung alveolar septal cells are undergoing both continuous apoptosis and proliferation. Whereas lung cell apoptosis has been recognized in human emphysema, little is known about cell proliferation.

Methods

Using a novel rat model of emphysema, induced by intratracheal instillation of cigarette smoke extract (CSE), we investigated the dynamics of emphysematous lung destruction. Emphysematous lung destruction was determined by measuring mean linear intercept and destructive index. Lung injury and repair were assessed by immunohistochemistry and Western blot analysis for active caspase-3 and proliferating cell nuclear antigen (PCNA) after 4, 8, and 12 weeks of CSE instillations.

Results

The emphysematous lung tissue destruction was present at 4 weeks of CSE treatment and progressed to 8 weeks. Spontaneous repair began at 12 weeks. Treatment with a peroxisome proliferator activated receptor (PPAR)α+γ agonist or granulocyte and macrophage-colony stimulating factor (GM-CSF) for 4 weeks prevented the progression of emphysematous lung destruction and decreased the number of caspase-3-positive cells.

Conclusion

Apoptosis and cell proliferation occur in this new model of emphysema. Treatment with a PPARα+γ agonist or GM-CSF can inhibit the progression of emphysematous alveolar septal destruction by decreasing alveolar cell apoptosis.

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Acknowledgment

This work was supported by a NIH grant [NIH ROI HL 72235 (NFV)], the Bixler Family COPD Foundation (AHA SDG 0735388 N), and an annual grant provided by Glaxo-Smith-Kline (King of Prussia, PA).

Conflict of interest

Authors in the manuscript has no conflict of interest.

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Authors and Affiliations

  1. Division of Pulmonary Science and Critical Care Medicine, University of Colorado School of Medicine, Denver, CO, 80262, USA

    Ji-Hyun Lee, Masayuki Hanaoka, Yoshiaki Kitaguchi, Donatas Kraskauskas, Leland Shapiro, Norbert F. Voelkel & Laima Taraseviciene-Stewart

  2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Bundang CHA Hospital, CHA University School of Medicine, Seongnam, Kyunggi-do, Korea

    Ji-Hyun Lee

  3. Division of Pulmonary and Critical Care Medicine, The Victoria Johnson Center for Emphysema Research, Virginia Commonwealth University, Richmond, VA, 23284, USA

    Norbert F. Voelkel

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  1. Ji-Hyun Lee
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  2. Masayuki Hanaoka
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  3. Yoshiaki Kitaguchi
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Correspondence to Ji-Hyun Lee.

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Lee, JH., Hanaoka, M., Kitaguchi, Y. et al. Imbalance of Apoptosis and Cell Proliferation Contributes to the Development and Persistence of Emphysema. Lung 190, 69–82 (2012). https://doi.org/10.1007/s00408-011-9326-z

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  • DOI: https://doi.org/10.1007/s00408-011-9326-z

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