Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes.
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.
Ferrari-Lacraz
S
S
Division of Immunology and Allergy, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
Nicod
L P
LP
Chicheportiche
R
R
Welgus
H G
HG
Dayer
J M
JM
D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000201:enzymology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D014176:Protein Biosynthesis / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
D007375:Interleukin-1; D008565:Membrane Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1