Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease

Am J Respir Cell Mol Biol. 2002 May;26(5):602-9. doi: 10.1165/ajrcmb.26.5.4685.


Destruction of lung elastin is critical for development of emphysema associated with chronic obstructive pulmonary disease (COPD). Lung macrophages release elastolytic enzymes, including matrix metalloproteinase (MMP)-9, along with tissue inhibitors of MMP (TIMP). We examined the production and activity of macrophage-derived MMP-9 and TIMP-1 from alveolar macrophages (AM) from smokers with COPD, healthy smokers (HS), and nonsmokers (NS). AM were stimulated with either lipopolysaccharide (LPS), interleukin (IL)-1 beta, or cigarette smoke-conditioned culture medium (CSM). AM from patients with COPD released greater amounts of MMP-9 with greater enzymatic activity than HS and NS. In contrast, AM from NS released more TIMP-1 than cells from HS and subjects with COPD. LPS and IL-1 beta caused a dose-dependent increase in MMP-9 release and activity, together with increased levels of TIMP-1. Dexamethasone prevented the increase in MMP-9 release, and increased TIMP-1 release. CSM increased MMP-9 and TIMP-1 release from AM of all groups. Dexamethasone decreased CSM-stimulated MMP-9 release, but had no effect on MMP-9 activity This study suggests that macrophages might be important in the development of COPD because these cells exhibit increased levels of elastolytic activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Enzyme Activation / drug effects
  • Female
  • Glucocorticoids / pharmacology
  • Humans
  • Interleukin-1 / pharmacology
  • Lipopolysaccharides / pharmacology
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / metabolism*
  • Male
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Smoking / metabolism
  • Smoking / pathology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis*
  • Tobacco Smoke Pollution


  • Culture Media, Conditioned
  • Glucocorticoids
  • Interleukin-1
  • Lipopolysaccharides
  • Tissue Inhibitor of Metalloproteinase-1
  • Tobacco Smoke Pollution
  • Dexamethasone
  • Matrix Metalloproteinase 9