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Multinucleate giant cells release functionally unopposed matrix metalloproteinase-9 in vitro and in vivo

Xing Wu Zhu1, Nicholas M Price, Robert H Gilman

  • 1Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, London, W12 0NN, England.

The Journal of Infectious Diseases
|September 1, 2007
PubMed

Insights

Multinucleated giant cells (MGCs) secrete significantly more matrix metalloproteinase-9 (MMP-9) than macrophages. This suggests MGCs contribute to tissue damage in tuberculosis.

Area of Science:

  • Immunology
  • Cell Biology
  • Pathology

Background:

  • Multinucleated giant cells (MGCs) are hallmarks of granulomatous inflammation.
  • Matrix metalloproteinase-9 (MMP-9), derived from monocytes, plays a crucial role in inflammatory tissue damage.

Purpose of the Study:

  • To investigate the secretion levels of MMP-9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP)-1, by MGCs.
  • To determine the role of MGCs in MMP-9 secretion during tuberculosis.

Main Methods:

  • Quantification of MMP-9 and TIMP-1 secretion by MGCs in vitro.
  • Analysis of MMP-9 and TIMP-1 expression in tuberculous lymph-node biopsy samples.

Main Results:

  • MGCs secreted significantly higher levels of MMP-9 (153 ng/mL) compared to macrophages (115 ng/mL) at 72 hours.
  • MGCs exhibited lower levels of TIMP-1 secretion.
  • High MMP-9 expression was observed in MGCs within tuberculous lymph nodes, particularly near necrotic areas, with undetectable TIMP-1.

Conclusions:

  • Mature MGCs are significant sources of MMP-9 secretion.
  • MGCs may contribute to inflammatory tissue damage in human tuberculosis through elevated MMP-9 levels.

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