Article: article from journal or magazin.
Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes.
American Journal of Respiratory Cell and Molecular Biology
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.
CD40 Ligand/metabolism, Cell Communication/immunology, Cell Membrane/immunology, Cell Membrane/metabolism, Gene Expression/immunology, Humans, Interleukin-1/antagonists & inhibitors, Interleukin-1/immunology, 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, Tissue Inhibitor of Metalloproteinase-1/genetics, Tissue Inhibitor of Metalloproteinase-1/metabolism, Tumor Necrosis Factor-alpha/antagonists & inhibitors, Tumor Necrosis Factor-alpha/immunology
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