Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction
Alternatively activated alveolar macrophages in pulmonary fibrosis-mediator production and intracellular signal transduction
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DOI：
10.1016/j.clim.2010.06.017
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发表时间：
2010-10-01
影响因子：
8.6
通讯作者：
Zissel, Gernot
中科院分区：
文献类型：
--
作者：
Pechkovsky, Dmitri V.;Prasse, Antje;Zissel, Gernot
根据其炎症反应模式，活化的巨噬细胞被表征为M1和M2。我们分析了细胞因子驱动分化过程中M2标记物的表达和细胞内信号转导。我们发现肺纤维化患者肺泡巨噬细胞自发产生趋化因子CCL17、CCL18和CCL22，并增加CD206的表达。在体外用Th2细胞因子IL-4和/或IL-10刺激正常人AM，发现IL-4是AM和单核细胞中最强大的m2表型诱导剂。重要的是，IL-10以协同方式增强il -4诱导的CCL18和IL-1RA的表达。IL-4/IL-10刺激可诱导纤维化患者AM中STAT3的强烈激活。这些结果表明，M2极化AM在肺纤维化的发病机制中起重要作用，并表明IL-4和IL-10都可以解释人类AM向M2表型转移，正如在纤维化间质性肺疾病患者中所见。(C) 2010爱思唯尔公司版权所有。
Activated macrophages have been characterized as M1 and M2 according to their inflammatory response pattern. Here we analyzed the M2 marker expression and intracellular signal transduction in the course of cytokine-driven differentiation. We found elevated spontaneous production of the chemokines CCL17, CCL18 and CCL22 and increased expression of CD206 by alveolar macrophages from patients with lung fibrosis. Stimulation of normal human AM with Th2 cytokines IL-4 and/or IL-10 in vitro revealed IL-4 as the most powerful inducer of M2-phenotype in AM and monocytes. Importantly, IL-10 enhanced IL-4-induced expression of CCL18 and IL-1RA in a synergistic fashion. IL-4/IL-10 stimulation induces a strong activation of STAT3 in AM from fibrosis patients. These results suggest an important role for M2 polarized AM in the pathogenesis of pulmonary fibrosis and indicate that both IL-4 and IL-10 account for human AM phenotype shift to M2, as seen in patients with fibrotic interstitial lung diseases. (C) 2010 Elsevier Inc. All rights reserved.