Increased Levels of Cell Death and Proliferation in Alveolar Wall Cells in Patients With Pulmonary Emphysema

doi:10.1378/chest.125.2.626

Chest

Volume 125, Issue 2, February 2004, Pages 626-632

https://doi.org/10.1378/chest.125.2.626 Get rights and content

Background

Pulmonary emphysema, a major component of COPD, is pathologically characterized by destructive alterations in pulmonary architectures as a result of persistent inflammation. However, alterations in the turnover of pulmonary cells are less well understood. This study was designed to examine whether the turnover of alveolar wall cells is altered in patients with emphysema.

Patients and measurements

We obtained lung tissue specimens from patients with emphysema who had undergone lung volume reduction surgery (13 patients) as well as asymptomatic smokers (7 patients) and nonsmokers (9 patients) undergoing lung resections for solitary lung cancers. Paraffin-embedded lung tissue sections were evaluated for apoptosis and proliferation using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) or immunohistochemistry for Bax, proliferation cell nuclear antigen (PCNA), and topoisomerase IIα. Tissue sections were also immunostained for epithelial membrane antigen, surfactant protein A, and CD31.

Results

The percentages of alveolar wall cells undergoing apoptosis and proliferation of the total number of alveolar wall cells were significantly higher in patients with emphysema than in asymptomatic smokers and nonsmokers (p < 0.05). The percentage of TUNEL-positive alveolar wall cells was positively correlated with the percentage of PCNA-positive alveolar wall cells. Most of the TUNEL-positive and PCNA-positive cells were alveolar epithelial cells.

Conclusions

These results suggest that the turnover of alveolar wall cells is enhanced in emphysematous lungs, compared to healthy lungs. Emphysema may be a dynamic disease process in which alveolar wall cell death and proliferation are repeated.

Section snippets

Subjects

The following three groups of patients were examined: 13 patients with emphysema; 7 asymptomatic smokers; and 9 asymptomatic nonsmokers. Lung tissue blocks were obtained from the patients with emphysema during lung volume reduction surgery. Lung tissue blocks were obtained from the asymptomatic smokers and the nonsmokers during lung resections for localized lung cancer. The characteristics of the patients are given in Table 1. This study's protocol conformed to the Declaration of Helsinki, and

Clinical Characteristics of Patients

As shown in Table 1, patients with emphysema had lower values of FEV₁ percent predicted and FEV₁/FVC ratio than asymptomatic smokers and nonsmokers (p < 0.01). In addition, patients with emphysema had smoked cigarettes for a higher number of pack-years than had asymptomatic smokers (p < 0.05). Both patients with emphysema and asymptomatic smokers had quit smoking at least 1 month before undergoing the operation. No differences in age were observed among the groups.

Histologic Detection of Apoptosis and Proliferation of Alveolar Wall Cells

Hematoxylin-eosin staining of

Discussion

In the present study, we demonstrated that the percentages of alveolar wall cells undergoing apoptosis and proliferation of the total number of alveolar wall cells are higher in patients with pulmonary emphysema than in asymptomatic smokers and nonsmokers. Apoptosis and proliferation in alveolar wall cells were assessed carefully using different methods. Since TUNEL, a marker for apoptotic cells, is known to be positive in some necrotic cells,⁹ we also examined the expression of the

ACKNOWLEDGMENT

We are grateful to the following participants in this study: Hiroshi Date and Tetsuji Fukuhara (Second Department of Surgery, Okayama University); Masato Minami (First Department of Surgery, Osaka University); Takayuki Shirakusa and Akinori Iwasaki (Second Department of Surgery, Fukuoka University); Yoshinosuke Fukuchi, MD (Department of Respiratory Medicine, Juntendo University); Takao Takizawa and Toshihide Shimizu (Saiseikai-Kurihashi Hospital); Kazuo Sugi (Sanyo National hospital); Hiroshi

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: This work was supported by a Grant-in-Aid for Scientific Research (No. 12670580) from the Ministry of Education, Science and Culture, Japan, and The Respiratory Failure Research Group in Japan.

^†: Dr. Takayuki Kuriyama (Professor, Department of Respiratory Medicine, Chiba University School of Medicine, Japan) is the director of the Respiratory Research Group in Japan.

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Chest

Laboratory and Animal InvestigationsIncreased Levels of Cell Death and Proliferation in Alveolar Wall Cells in Patients With Pulmonary Emphysema

Background

Patients and measurements

Results

Conclusions

Section snippets

Subjects

Clinical Characteristics of Patients

Histologic Detection of Apoptosis and Proliferation of Alveolar Wall Cells

Discussion

ACKNOWLEDGMENT

Life Sci

Chronic obstructive pulmonary disease: risk factors, pathophysiology, and pathogenesis

Annu Rev Med

Endothelial cell death and decreased expression of vascular endothelial cell growth factor and vascular endothelial growth factor receptor 2 in emphysema

Am J Crit Care Med

Upregulation of gelatinase A and B, collagenase 1 and 2, and increased parenchymal cell death in COPD

Chest

Alveolar wall apoptosis induces lung destruction and emphysematous changes

Am J Respir Cell Mol Biol

Apoptosis versus proliferation activities and relative mechanism in chronic obstructive pulmonary disease

Zhonghua Yi Xue Za Zhi

Elastase-induced emphysema: asynchronous bronchial, alveolar and endothelial cell proliferation during the acute response to injury

J Pathol

Cigarette smoke causes rapid cell proliferation in small airways and associated pulmonary arteries

Am J Physiol

Laboratory and Animal Investigations
Increased Levels of Cell Death and Proliferation in Alveolar Wall Cells in Patients With Pulmonary Emphysema