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

Background: Several matrix metalloproteinases ( MMPs) 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. A study was undertaken to investigate the role of MMP-12 in the development of COPD in human smokers. Methods: Induced sputum samples were collected from patients with stable COPD (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 than in 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 patients with COPD than in controls (4.11 (1.4 - 8.0) v 0.14 (0.1 - 0.2) mu g/ml, p = 0.0002). Conclusion: MMP-12 is markedly increased in induced sputum from patients with stable COPD compared with controls, suggesting a role for MMP-12 in the development of COPD in smokers.