Human Lung Tissue Macrophages, but Not Alveolar Macrophages, Express Matrix Metalloproteinases After Direct Contact With Activated T Lymphocytes

Am J Respir Cell Mol Biol. 2001 Apr;24(4):442-51. doi: 10.1165/ajrcmb.24.4.4008.


Human alveolar macrophages (AM) and lung tissue macrophages (LTM) have a distinct localization in the cellular environment. We studied their response to direct contact with activated T lymphocytes in terms of the production of interstitial collagenase (MMP-1), 92-kD gelatinase (MMP-9), and of TIMP-1, one of the counter-regulatory tissue inhibitors of metalloproteinases. Either AM obtained by bronchoalveolar lavage or LTM obtained by mincing and digestion of lung tissue were exposed for 48 h to plasma membranes of T lymphocytes previously activated with phorbol myristate acetate and phytohemagglutinin for 24 h. Membranes of activated T cells strongly induced the production of MMP-1, MMP-9, and TIMP-1 exclusively in LTM but not in AM, whereas membranes from unstimulated T cells failed to induce the release of MMPs. Both populations of mononuclear phagocytes spontaneously released only small amounts of MMPs and TIMP-1. Similar results were obtained when MMP and TIMP-1 expression was analyzed at pretranslational and biosynthetic levels, respectively. Blockade experiments with cytokine antagonists revealed the involvement of T-cell membrane-associated interleukin-1 and tumor necrosis factor-alpha in MMP production by LTM upon contact with T cells. These data suggest that the ability of lung macrophages to produce MMPs after direct contact with activated T cells is related to the difference in phenotype of mononuclear phagocytes and cell localization. In addition, these observations indicate that cell-cell contact represents an important biological mechanism in potentiating the inflammatory response of mononuclear phagocytes in the lungs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD40 Ligand / metabolism
  • Cell Communication / immunology*
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Gene Expression / immunology
  • Humans
  • In Vitro Techniques
  • Interleukin-1 / antagonists & inhibitors
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism
  • Lung / cytology
  • Lung / immunology
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / enzymology*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • Phagocytosis / immunology
  • Protein Biosynthesis / physiology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Interleukin-1
  • Membrane Proteins
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • CD40 Ligand
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 1