Elevated MMP-12 protein levels in induced sputum from COPD patients.

Background: Several Matrix Metalloproteinases (MMP’s) are involved in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). In mice, MMP-12 plays a crucial role in the development of cigarette smoke induced emphysema. The main purpose of this study was to investigate the role of MMP-12 in the development of COPD in human smokers. Methods: Induced sputum samples were collected from stable COPD patients (n = 28), healthy smokers (n = 14), never smokers (n = 20) and former smokers (n = 14). MMP-12 protein levels in induced sputum were determined by ELISA and compared between the four study groups. MMP-12 enzymatic activity in induced sputum was evaluated by casein zymography and by cleaving of a fluorescence-quenched substrate. Results: Median (IQR) MMP-12 levels were significantly higher in COPD patients when compared to healthy smokers, never smokers and former smokers (17.5 (7.1-42.1) v 6.7 (3.9-10.4) v 4.2 (2.4-11.3) v 6.1 (4.5-7.6) ng/ml, p = 0.0002). MMP-12 enzymatic activity was significantly higher in COPD patients compared to controls (4.11 (1.4-8.0) v 0.14 (0.1-0.2) µg/µl respectively, p = 0.0002). Conclusion: MMP-12 is markedly increased in induced sputum from stable COPD patients when compared to controls, suggesting a role for MMP-12 in the development of COPD in smokers.

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