Elevated MMP-12 protein levels in induced sputum from patients with COPD
- I K Demedts1,
- A Morel-Montero2,
- S Lebecque3,
- Y Pacheco3,
- D Cataldo4,
- G F Joos1,
- R A Pauwels1,†,
- G G Brusselle1
- 1Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
- 2Immunotech, Beckman Coulter, Marseille, France
- 3Service de Pneumologie, CHU-Lyon, France
- 4Department of Pneumology, University of Liege and CHU Liege, Liege, Belgium
- Correspondence to:
Dr I K Demedts
Department of Respiratory Diseases, Ghent University Hospital 7K12-IE, De Pintelaan 185, B-9000 Ghent, Belgium;
- Received 15 April 2005
- Accepted 21 November 2005
- Published Online First 24 November 2005
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) μg/μl, 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.
- BAL, bronchoalveolar lavage
- COPD, chronic obstructive pulmonary disease
- DTT, dithiotreitol
- ECM, extracellular matrix
- ELISA, enzyme linked immunosorbent assay
- FEV1, forced expiratory volume in 1 second
- FVC, forced vital capacity
- GOLD, Global Initiative for Chronic Obstructive Lung Disease
- ICS, inhaled corticosteroids
- IFN-γ, interferon-γ
- IL-13, interleukin-13
- MMP, matrix metalloproteinase
- PBS, phosphate buffered saline
- TGF-β1, transforming growth factor β1
- TNF-α, tumour necrosis factor α
↵† Deceased 3 January 2005
Published Online First 24 November 2005
This work was supported by the Fund for Scientific Research in Flanders (FWO Vlaanderen, Research Projects G.0011.03 and G.0343.01N) and by project grant 01251504 from the Concerted Research Initiative of the Ghent University. ID is a doctoral research fellow of the Fund for Scientific Research in Flanders (FWO Vlaanderen).
Competing interests: none declared.