title: Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo.
abstract: Multinucleated giant cells (MGCs) are characteristic of granulomatous inflammation. Matrix metalloproteinase (MMP)-9, the major monocyte-derived matrix metalloproteinase, is key in inflammatory tissue damage. At 72 h, MGCs secrete 153 +/- 2.5 ng/mL MMP-9, compared with 115 +/- 3.8 ng/mL during macrophage differentiation (P<.05). In contrast, the level of MGC secretion-specific tissue inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, is lower (P<.05). Mature MGCs secrete constitutively greater concentrations of MMP-9 than do monocytes or macrophages (P<.05). MGCs in tuberculous lymph-node biopsy samples express high MMP-9 levels adjacent to areas of necrosis, whereas TIMP-1 is not detected. Thus, MGCs are potentially important sources of MMP-9 secretion and may contribute to inflammatory tissue damage in human tuberculosis.
authors.affiliation: Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, W12 0NN, England.
authors.forename: Xing Wu
authors.initials: XW
authors.lastname: Zhu
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Price
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.forename: Sixto
authors.initials: S
authors.lastname: Recarvarren
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D015726:Giant Cells / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009169:Mycobacterium tuberculosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014375:Tuberculoma / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D014388:Tuberculosis, Lymph Node / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9