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 di stinct localization in the cellular environment. We studied their response to direct contact with activated T lymphocytes in terms of the production o f interstitial collagenase (MMP-1), 92-kD gelatinase (MMP-9), and of TIMP-1 , one of the counter-regulatory tissue inhibitors of metalloproteinases. Ei ther AM obtained by bronchoalveolar lavage or LTM obtained by mincing and d igestion of lung tissue were exposed for 48 h to plasma membranes of T lymp hocytes previously activated with phorbol myristate acetate and phytohemagg lutinin for 24 h. Membranes of activated T cells strongly induced the produ ction 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 smal l amounts of MMPs and TIMP-1, Similar results were obtained when MMP and TI MP-1 expression was analyzed at pretranslational and biosynthetic levels, r espectively. Blockade experiments with cytokine antagonists revealed the in volvement of T-cell membrane-associated interleukin-l and tumor necrosis fa ctor-a in MMP production by LTM upon contact with T cells. These data sugge st that the ability of lung macrophages to produce MMPs after direct contac t with activated T cells is related to the difference in phenotype of monon uclear phagocytes and cell localization. In addition, these observations in dicate that cell-cell contact represents an important biological mechanism in potentiating the inflammatory response of mononuclear phagocytes in the lungs.