Chest
Volume 132, Issue 6, December 2007, Pages 1733-1740
Journal home page for Chest

Original Research
COPD
Matrix Metalloproteinase-2 Protein in Lung Periphery Is Related to COPD Progression

https://doi.org/10.1378/chest.06-2819Get rights and content

Background

There is increasing evidence that matrix metalloproteinases (MMPs) may contribute to the pathogenesis of COPD, but their role in humans is not completely understood. We performed this study to quantify the expression of MMP-2 in a population of COPD patients at different stages of severity.

Methods

We collected surgical specimens from 46 subjects, as follows: 10 smokers with severe COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage III-IV); 13 smokers with mild/moderate COPD (GOLD stage I-II); 12 control smokers; and 11 nonsmoking control subjects. We quantified MMP-2 expression in alveolar macrophages, alveolar walls, peripheral airways, and pulmonary arterioles by immunohistochemistry.

Results

In all compartments, MMP-2 expression was increased both in smokers with severe COPD and in smokers with mild/moderate COPD compared to control smokers and nonsmokers (p < 0.05 for all comparisons). Only in alveolar macrophages was MMP-2 expression increased in smokers with severe COPD compared to smokers with mild/moderate COPD (p = c0.002). Moreover, MMP-2 expression was inversely related to values of FEV1/FVC ratio (p < 0.0001; r = −0.71) and Pao2 (in millimeters of Hg) [p = 0.005; r = −0.49], and was positively related to emphysema score (p = 0.01; r = 0.65) and residual volume percent predicted (p = 0.04; r = 0.49). A stepwise increase in the total number of alveolar macrophages was observed in the four groups of subjects examined, with the highest value in those with severe COPD.

Conclusion

This study shows that MMP-2 expression in the lung periphery progressively increases as lung function worsens and the degree of emphysema increases. These results suggest that MMP-2 may be a key mediator of the mechanisms leading to lung tissue remodeling and inflammation in patients with severe COPD.

Section snippets

Study Population

To quantify the expression of MMP-2, we collected lung tissue from 46 subjects undergoing surgery for appropriate clinical indications (ie, lung volume reduction surgery for the treatment of severe emphysema or lung resection for a solitary peripheral carcinoma). The subjects were categorized into the following four groups: smokers with severe COPD (GOLD stage III-IV [ie, FEV1/FVC ratio, < 70%; FEV1, < 50% predicted]; n = 10); smokers with mild/moderate COPD (GOLD stage I–II [ie, FEV1/FVC

Results

Table 1shows the clinical characteristics of the subjects examined. The complete analysis of clinical and functional parameters is reported in Web-only material.

As for MMP-2 immunoreactivity, a prominent staining was observed in alveolar macrophages and alveolar walls (Fig 1), as well as in peripheral airways, and pulmonary arterioles, where it was mainly associated with smooth muscle bundles. The percentage of MMP-2+ macrophages differed significantly among the four groups of subjects examined

Discussion

This study shows that in patients with COPD there is a marked up-regulation of MMP-2 in the lung periphery that is related to the degree of lung function impairment and emphysema. These results suggest that MMP-2 may be a key mediator of the mechanisms leading to lung tissue destruction in patients with severe COPD.

A number of animal models have illustrated the potential role of MMPs in the development of emphysema. In guinea pigs, exposure to cigarette smoke produces emphysematous changes that

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    This research was funded by the University of Padova, the Italian Ministry of University and Research (MUR), and by a grant from the European Respiratory Society (to Dr. Baraldo).

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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