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1 Dept of Biochemistry, Nippon Dental University, Chiyoda-ku, Tokyo, Japan. 2 Dept of Medicine, Divisions of Molecular Medicine, 3 Institute of Human Nutrition, 4 Pulmonary Medicine, and 5 Dept of Surgery, College of Physicians and Surgeons of Columbia University, New York, NY, USA. 6 Authors contributed equally to the study.
CORRESPONDENCE: J. M. D'Armiento, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, P&S 9-449, New York, NY 10032, USA. Fax: 1 2123055052. E-mail: jmd12@columbia.edu
Keywords: Caspase, cell death, cell proliferation, morphometry, terminal deoxynucleotide transferase-mediated dUTP nick-end labelling
Received: February 24, 2004
Accepted October 15, 2004
Pulmonary emphysema is associated with alterations in matrix proteins and protease activity. These alterations may be linked to programmed cell death by apoptosis, potentially influencing lung architecture and lung function.
To evaluate apoptosis in emphysema, lung tissue was analysed from 10 emphysema patients and six individuals without emphysema (normal). Morphological analysis revealed alveolar cells in emphysematous lungs with convoluted nuclei characteristic of apoptosis. DNA fragmentation was detected using terminal deoxynucleotide transferase-mediated dUTP nick-end labelling (TUNEL) and gel electrophoresis. TUNEL revealed higher apoptosis in emphysematous than normal lungs. Markers of apoptosis, including active caspase-3, proteolytic fragment of poly (ADP-ribose) polymerase, Bax and Bad, were detected in emphysematous lungs. Linear regression showed that apoptosis was inversely correlated with surface area. Emphysematous lungs demonstrated lower surface areas and increased cell proliferation. There was no correlation between apoptosis and proliferation, suggesting that, although both events increase during emphysema, they are not in equilibrium, potentially contributing to reduced lung surface area.
In summary, cell-based mechanisms associated with emphysematous parenchymal damage include increased apoptosis and cell proliferation. Apoptosis correlated with airspace enlargement, supporting epidemiological evidence of the progressive nature of emphysema. These data extend the understanding of cell dynamics and structural changes within the lung during emphysema pathogenesis.
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