MMP-9 protein level does not reflect overall MMP activity in the airways of patients with COPD

Respir Med. 2008 Jun;102(6):845-51. doi: 10.1016/j.rmed.2008.01.006. Epub 2008 Mar 6.


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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Bronchoalveolar Lavage Fluid / chemistry
  • Collagenases / metabolism
  • Female
  • Forced Expiratory Volume
  • Gelatinases / metabolism
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Pancreatic Elastase / metabolism
  • Pulmonary Disease, Chronic Obstructive / enzymology*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Sputum / enzymology
  • Sputum / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Vital Capacity


  • Biomarkers
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Pancreatic Elastase
  • Collagenases
  • Gelatinases
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9