Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Segura-Valdez
L
L
Instituto Nacional de Enfermedades Respiratorias (Drs. Segura-Valdez, Gaxiola, Selman, and Ms. Becerril), Mexico City, Mexico.
Pardo
A
A
Gaxiola
M
M
Uhal
B D
BD
Becerril
C
C
Selman
M
M
D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D017364:Collagenases / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008168:Lung / Q000473:pathology*; D008173:Lung Diseases, Obstructive / Q000473:pathology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology
D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1