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Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma
S V Culpitt1, D F Rogers, S L Traves
1Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College London, Dovehouse Street, London SW3 6LY, UK.
Abstract:
Asthma and chronic obstructive pulmonary disease (COPD) are different conditions with contrasting airway inflammation and parenchymal disease patterns. A number of matrix metalloproteases (MMPs) are implicated in the pathophysiology of COPD and asthma. Different profiles of airway MMPs may, therefore, be expected in asthma and COPD. The present study compared MMP profiles in the airways of non-smokers, non-symptomatic cigarette smokers, and patients with COPD or asthma (n = 15 subjects per group). Induced sputum was assessed for MMP-1, -2, -3, -8 and -9, and tissue inhibitor of metalloproteases (TIMP)-1 by ELISA. Gelatinase activity was determined by zymography. Sputum from COPD patients contained increased levels of MMP-1, -8 and -9 compared with the other groups (2-7-fold, depending upon group). MMP-9 activity was elevated in COPD sputum by 3-12-fold above the other groups. Sputum from COPD patients had 3-fold higher levels of TIMP-1 than samples from asthmatics or controls, but was not different to smokers. FEV1 correlated negatively with MMP-1, -8, -9, MMP-9 activity and TIMP-1, whereas percent neutrophils in sputum correlated positively with MMP-1, -8, -9, TIMP-1 and MMP-9 activity. The MMP profile in COPD differs to that in asthma and cigarette smokers. This may contribute to, or be a marker of, different pathophysiologies of asthma and COPD.
Insights
Matrix metalloproteases (MMPs) differ in chronic obstructive pulmonary disease (COPD) airways compared to asthma. COPD airways show higher MMP-1, -8, -9 levels and activity, potentially marking distinct disease paths.
Area of Science:
- Pulmonary Medicine
- Biochemistry
Background:
- Asthma and COPD are distinct respiratory diseases with differing inflammatory pathways.
- Matrix metalloproteases (MMPs) play a role in the pathology of both asthma and COPD.
- Distinct MMP profiles in airways may reflect the unique pathophysiology of each condition.
Purpose of the Study:
- To compare matrix metalloprotease (MMP) profiles in induced sputum from non-smokers, smokers, COPD patients, and asthma patients.
- To investigate the relationship between MMP levels, lung function (FEV1), and sputum neutrophil percentage in COPD.
Main Methods:
- Induced sputum was collected from four groups: non-smokers, non-symptomatic smokers, COPD patients, and asthma patients (n=15 per group).
- Levels of MMP-1, -2, -3, -8, -9, and TIMP-1 were quantified using ELISA.
- Gelatinase activity was assessed by zymography.
- Spirometry (FEV1) and sputum differential cell counts were performed.
Main Results:
- COPD patients exhibited significantly higher sputum levels of MMP-1, -8, and -9 (2-7 fold increase) compared to other groups.
- MMP-9 activity was markedly elevated in COPD sputum (3-12 fold increase).
- TIMP-1 levels were 3-fold higher in COPD patients than asthmatics or controls, but similar to smokers.
- FEV1 negatively correlated with MMP-1, -8, -9, MMP-9 activity, and TIMP-1.
- Sputum neutrophil percentage positively correlated with MMP-1, -8, -9, TIMP-1, and MMP-9 activity.
Conclusions:
- The MMP profile in COPD airways is distinct from that observed in asthma and healthy smokers.
- Elevated MMPs and TIMP-1 in COPD sputum may indicate specific pathophysiological mechanisms.
- These MMP profiles could serve as biomarkers for differentiating the underlying pathologies of COPD and asthma.
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