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 inflammati on coexisting with an abnormal protease/antiprotease balance. However, the possible role of different serine and metalloproteinases remains controvers ial. Patients and measurements: We examined the expression of gelatinases A and B (matrix metalloproteinase [MMP]-2 and MMP-9); collagenases 1, 2, and 3 (M MP-1, MMP-8, and MMP-13); as well as the presence of apoptosis in lung tiss ues of 10 COPD patients and 5 control subjects. In addition, gelatinase-h a nd gelatinase-B activities were assessed in BAL obtained from eight COPD pa tients, and from six healthy nonsmokers and sis healthy smoker control subj ects. Setting: Tertiary referral center and university laboratories of bioc hemistry, and lung cell kinetics. Results: Immunohistochemical analysis of COPD lungs showed a markedly incre ased expression of collagenases 1 and 2, and gelatinases A and B, while col lagenase 3 was not found. Neutrophils exhibited a positive signal for colla genase 2 and gelatinase B, whereas collagenase 1 and gelatinase A were reve aled mainly in macrophages and epithelial cells. BAL gelatin zymography sho wed a moderate increase of progelatinase-A activity and intense bands corre sponding to progelatinase B, In situ end labeling of fragmented DNA display ed foci of positive endothelial cells, although some alveolar epithelial, i nterstitial, and inflammatory cells also revealed intranuclear staining. Conclusion: These findings suggest that there is an upregulation of collage nase 1 and 2 and gelatinases A and B, and an increase in endothelial and ep ithelial cell death, which may contribute to the pathogenesis of COPD throu gh the remodeling of airways and alveolar structures.