Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes
Human lung tissue macrophages, but not alveolar macrophages, express matrix metalloproteinases after direct contact with activated T lymphocytes
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DOI：
10.1165/ajrcmb.24.4.4008
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发表时间：
2001-04-01
影响因子：
6.4
通讯作者：
Dayer, JM
中科院分区：
文献类型：
--
作者：
Ferrari-Lacraz, S;Nicod, LP;Dayer, JM
人肺泡巨噬细胞（AM）和肺组织巨噬细胞（LTM）在细胞环境中具有不同的定位。我们研究了它们对直接接触活化T淋巴细胞的反应，包括间质胶原酶（MMP-1）、92-kD明胶酶（MMP-9）和金属蛋白酶的反调节组织抑制剂TIMP-1的产生。将支气管肺泡灌洗获得的AM或切碎和消化肺组织获得的LTM暴露于预先用佛波醇肉豆蔻酸酯乙酸酯和植物血凝素活化24 h的T淋巴细胞质膜48 h。膜的活化T细胞强烈诱导MMP-1，MMP-9，TIMP-1的生产只在LTM，但不是在AM，而膜从未刺激的T细胞未能诱导MMP的释放。这两个群体的单核吞噬细胞自发地释放只有少量的MMP和TIMP-1，类似的结果时，MMP和TIMP-1的表达进行了分析，分别在翻译前和生物合成水平。用细胞因子拮抗剂的阻断实验揭示了在与T细胞接触时，T细胞膜相关的白细胞介素-1和肿瘤坏死因子-α参与LTM的MMP产生。这些数据表明，肺巨噬细胞与活化的T细胞直接接触后产生MMPs的能力与单核吞噬细胞表型和细胞定位的差异有关。此外，这些观察结果表明，细胞-细胞接触代表了增强肺部单核吞噬细胞炎症反应的重要生物学机制。
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-l and tumor necrosis factor-a 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.