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
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.