Matrix metalloproteinases -8, -9 and -12 in smokers and patients with Stage 0 COPD

Abstract

COPD is underdiagnosed and its early assessment is problematic. It has been suggested that symptomatic smokers with normal FEV₁/FVC (Stage 0 COPD, GOLD criteria) can develop COPD in the future. Potential early biomarkers in COPD include the matrix metallo-proteinases (MMPs). It is not yet known, whether alterations in MMP expression are associated with smoking alone or with the risk of developing COPD. In this cross-sectional study MMP-8, MMP-9 and MMP-12 were determined from induced sputum and plasma by ELISA, immunocytochemistry, zymography, and/or Western blot in non-smokers (n = 32), smokers with symptoms (Stage 0, GOLD criteria) (n = 23) or without symptoms (n = 23). Only MMP-8 differentiated Stage 0 COPD from non-symptomatic smokers (p = 0.02). MMP-9 levels were significantly elevated in the induced sputum of non-symptomatic smokers and Stage 0 COPD (p = 0.01, p < 0.001) compared to non-smokers, but did not differ between the two subgroups of smokers. MMP-12 was higher only at Stage 0 compared to non-smokers (p = 0.04). MMP-8, MMP-9 and MMP-12 immunoreactivity was localized in macrophages and neutrophils, especially in smokers. MMP-8 levels correlated significantly with the small airway flow parameters (MEF50, MEF25) (p = 0.005 and p = 0.0004) and markers of neutrophil activation (myeloperoxidase, lactoferrin). In conclusion MMP-8 may differentiate Stage 0 from healthy smokers.

Keywords:

• cigarette smoking
• GOLD
• COPD
• MMP
• myeloperoxidase
• oxidant
• Stage 0

Acknowledgements

Tiina Marjomaa, Merja Luukkonen and Ritva Keva are acknowledged for their excellent technical assistance, Antero Kokkonen and the Jaakko Pöyry Company for helping us in the recruitment of the non-smokers and smokers. We are very grateful to every subject who agreed to participate in this study.

This work was supported by the Sigrid Juselius Foundation, The Finnish Antituberculosis Association Foundation, Jansson Foundation, the Helsinki University Hospital (HUCH-EVO), the Academy of Finland and the ERS COPD Travel Grant for Best Posters 2005.