HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS REGISTER		Author Keyword(s) Vol Page [Advanced]

This Article Full Text Full Text (PDF) All Versions of this Article: thx.2005.042432v1 61/3/196    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Demedts, I K Articles by Brusselle, G G Search for Related Content PubMed PubMed Citation Articles by Demedts, I K Articles by Brusselle, G G

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

,

¹ Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium
² Immunotech, Beckman Coulter, Marseille, France
³ Service de Pneumologie, CHU-Lyon, France
⁴ Department of Pneumology, University of Liege and CHU Liege, Liege, Belgium

Correspondence to:
Correspondence to:
Dr I K Demedts
Department of Respiratory Diseases, Ghent University Hospital 7K12-IE, De Pintelaan 185, B-9000 Ghent, Belgium; M.DemedtsIngelK{at}UGent.be

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.

Abbreviations: 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-, interferon-; IL-13, interleukin-13; MMP, matrix metalloproteinase; PBS, phosphate buffered saline; TGF-ß₁, transforming growth factor ß₁; TNF-, tumour necrosis factor

Keywords: chronic obstructive pulmonary disease; matrix metalloproteinases; induced sputum; MMP-12; smoking

This article has been cited by other articles:

				R. D. Gray, G. MacGregor, D. Noble, M. Imrie, M. Dewar, A. C. Boyd, J. A. Innes, D. J. Porteous, and A. P. Greening Sputum Proteomics in Inflammatory and Suppurative Respiratory Diseases Am. J. Respir. Crit. Care Med., September 1, 2008; 178(5): 444 - 452. [Abstract] [Full Text] [PDF]

				J. Xu, F. Xu, and E. Barrett Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L162 - L170. [Abstract] [Full Text] [PDF]

				C. L. Quement, I. Guenon, J.-Y. Gillon, V. Lagente, and E. Boichot MMP-12 induces IL-8/CXCL8 secretion through EGFR and ERK1/2 activation in epithelial cells Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1076 - L1084. [Abstract] [Full Text] [PDF]

				P. N. Black, P. S. T. Ching, B. Beaumont, S. Ranasinghe, G. Taylor, and M. J. Merrilees Changes in elastic fibres in the small airways and alveoli in COPD Eur. Respir. J., May 1, 2008; 31(5): 998 - 1004. [Abstract] [Full Text] [PDF]

				A. Churg, M. Cosio, and J. L. Wright Mechanisms of cigarette smoke-induced COPD: insights from animal models Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L612 - L631. [Abstract] [Full Text] [PDF]

				A. Churg, R. Wang, X. Wang, P.-O. Onnervik, K. Thim, and J. L Wright Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs Thorax, August 1, 2007; 62(8): 706 - 713. [Abstract] [Full Text] [PDF]

				T. Yoshida and R. M. Tuder Pathobiology of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Physiol Rev, July 1, 2007; 87(3): 1047 - 1082. [Abstract] [Full Text] [PDF]

				I. K. Demedts, K. R. Bracke, G. Van Pottelberge, D. Testelmans, G. M. Verleden, F. E. Vermassen, G. F. Joos, and G. G. Brusselle Accumulation of Dendritic Cells and Increased CCL20 Levels in the Airways of Patients with Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., May 15, 2007; 175(10): 998 - 1005. [Abstract] [Full Text] [PDF]

				P. J. Barnes, B. Chowdhury, S. A. Kharitonov, H. Magnussen, C. P. Page, D. Postma, and M. Saetta Pulmonary Biomarkers in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., July 1, 2006; 174(1): 6 - 14. [Abstract] [Full Text] [PDF]