Chest
Volume 117, Issue 3, March 2000, Pages 684-694
Journal home page for Chest

Clinical Investigations
COPD
Upregulation of Gelatinases A and B, Collagenases 1 and 2, and Increased Parenchymal Cell Death in COPD

https://doi.org/10.1378/chest.117.3.684Get rights and content

Background

A central feature in the pathogenesis of COPD is the inflammation coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controversial.

Patients and measurements

We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (MMP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tissues of 10 COPD patients and 5 control subjects. In addition, gelatinase-A and gelatinase-B activities were assessed in BAL obtained from eight COPD patients, and from six healthy nonsmokers and six healthy smoker control subjects.

Setting

Tertiary referral center and university laboratories of biochemistry, and lung cell kinetics.

Results

Immunohistochemical analysis of COPD lungs showed a markedly increased expression of collagenases 1 and 2, and gelatinases A and B, while collagenase 3 was not found. Neutrophils exhibited a positive signal for collagenase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were revealed mainly in macrophages and epithelial cells. BAL gelatin zymography showed a moderate increase of progelatinase-A activity and intense bands corresponding to progelatinase B. In situ end labeling of fragmented DNA displayed foci of positive endothelial cells, although some alveolar epithelial, interstitial, and inflammatory cells also revealed intranuclear staining.

Conclusion

These findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.

Section snippets

Study Population

We studied the expression and localization of immunoreactive MMP-1, MMP-2, MMP-8, MMP-9, and MMP-13 in paraffin-embedded lung tissues collected from 10 male individuals with COPD (group 1). Seven of them were obtained from autopsies of patients with prolonged and terminal lung disease (mean age ± SD, 66.8 ± 5.5 years), while the other three derived from lung volume reduction surgery (ages, 59, 56, and 55 years). Male individuals who died from causes other than lung diseases were used as control

Results

Mean ( ± SD) values of age, smoking history, and lung functional characteristics are shown in Table 1. All patients were heavy smokers and displayed severe airflow limitation, but no statistical differences were found in the functional respiratory tests of both groups. On microscopic examination, lung tissues of group 1 exhibited varied, but usually severe, airway inflammation, goblet cell hyperplasia, and focal squamous metaplasia. In peripheral airways, variable degrees of wall inflammation,

Discussion

COPD is a chronic respiratory disorder characterized by slowly progressive airflow obstruction. It usually occurs in heavy smokers, and it is associated with variable degrees of bronchial inflammation and mucus gland hyperplasia, small airway inflammation and fibrosis, and emphysema. Inflammation in COPD is a central and complex pathologic process involving different immune and inflammatory cells, although the precise role of each of them in the pathogenesis is still controversial. According to

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    This study was partially supported by PUIS-UNAM, and CONACYT Grant number F643-M9406.

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