Matrix metalloproteinase-2 protein in lung periphery is related to COPD progression.
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.


CONCLUSIONS
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.
Baraldo
Simonetta
S
Department of Cardiac, Thoracic, and Vascular Sciences, University of Padova, Via Giustiniani 3, Padova, Italy.
Bazzan
Erica
E
Zanin
Maria Elena
ME
Turato
Graziella
G
Garbisa
Spiridione
S
Maestrelli
Piero
P
Papi
Alberto
A
Miniati
Massimo
M
Fabbri
Leonardo M
LM
Zuin
Renzo
R
Saetta
Marina
M
D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology*; D012129:Respiratory Function Tests; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects; D018709:Statistics, Nonparametric
D020778:Matrix Metalloproteinase 2