Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo.
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.
Zhu
Xing Wu
XW
Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, W12 0NN, England.
Price
Nicholas M
NM
Gilman
Robert H
RH
Recarvarren
Sixto
S
Friedland
Jon S
JS
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
D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9