title: Release and activity of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by alveolar macrophages from patients with chronic obstructive pulmonary disease.
abstract: 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.
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College of Science, London, United Kingdom.
authors.forename: Richard E K
authors.initials: RE
authors.lastname: Russell
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Culpitt
authors.forename: Carmen
authors.initials: C
authors.lastname: DeMatos
authors.forename: Louise
authors.initials: L
authors.lastname: Donnelly
authors.forename: Michael
authors.initials: M
authors.lastname: Smith
authors.forename: John
authors.initials: J
authors.lastname: Wiggins
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis*; D014028:Tobacco Smoke Pollution
chemical_list: D017077:Culture Media, Conditioned; D005938:Glucocorticoids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019715:Tissue Inhibitor of Metalloproteinase-1; D014028:Tobacco Smoke Pollution; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9