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MMP-9 protein level does not reflect overall MMP activity in the airways of patients with COPD
Gillian E Lowrey1, Neil Henderson, John D Blakey
1Nottingham University Hospitals NHS Trust, Nottingham, UK.
Background:
Animal and human studies have implicated an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in the pathogenesis of chronic obstructive pulmonary disease (COPD). MMP-9 protein is increased in COPD and we hypothesized that total MMP activity would be raised although this has not previously been measured.
Methods:
Using fluorescence and biotin labelled MMP assays, RT-PCR, western blotting and enzyme-linked immunosorbent assay we examined total MMP activity, specific gelatinase, elastase, collagenase activity, TIMP-1 and TIMP-2 in induced sputum from smokers with COPD and smokers without COPD.
Results:
Induced sputum was obtained from 15 smokers with COPD and 14 smokers without COPD. MMP-9 levels were higher in those with COPD compared with controls (p<0.05). Total MMP activity, specific gelatinase, collagenase and elastase activities were not higher in COPD patients. In addition, reduced MMP activity was correlated with increasing airflow obstruction in COPD (p=0.016).
Conclusion:
MMP-9 protein but not MMP activity was higher in sputum of COPD patients compared with controls. These results suggest that MMP-9 levels may not reflect the overall MMP activity in the airways of patients with COPD suggesting a complex relationship between MMP-9 protein and activity. Further studies of MMPs in COPD should comprise activity measures in addition to protein levels.
Insights
Matrix metalloproteinase-9 (MMP-9) protein is elevated in chronic obstructive pulmonary disease (COPD), but total MMP activity is not. This suggests MMP-9 protein levels may not fully represent overall MMP activity in COPD airways.
Area of Science:
- Pulmonary Medicine
- Biochemistry
- Enzymology
Background:
- Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) imbalance is implicated in chronic obstructive pulmonary disease (COPD) pathogenesis.
- Elevated MMP-9 protein levels are observed in COPD patients.
Purpose of the Study:
- To investigate total MMP activity in the airways of COPD patients.
- To compare MMP activity and protein levels in smokers with and without COPD.
Main Methods:
- Analysis of induced sputum from smokers with and without COPD.
- Assays used: fluorescence and biotin-labelled MMP assays, RT-PCR, western blotting, ELISA.
- Measured parameters: total MMP activity, specific gelatinase, elastase, collagenase activity, TIMP-1, and TIMP-2.
Main Results:
- MMP-9 protein levels were significantly higher in COPD patients (p<0.05).
- Total MMP activity, specific gelatinase, collagenase, and elastase activities were not elevated in COPD patients.
- Reduced MMP activity correlated with increased airflow obstruction in COPD (p=0.016).
Conclusions:
- MMP-9 protein levels are higher in COPD sputum, but overall MMP activity is not.
- MMP-9 protein levels may not accurately reflect total MMP activity in COPD airways.
- Future COPD research should include MMP activity measurements alongside protein levels.
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