Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions

Nontransformed, GM-CSF-dependent macrophage lines are a unique model to study tissue macrophage functions
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DOI:
10.1073/pnas.1302877110
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发表时间:
2013-06-11
影响因子:
11.1
通讯作者:
Freudenberg, Marina A.
Freudenberg, Marina A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Fejer, Gyoergy;Wegner, Mareike Dorothee;Freudenberg, Marina A.

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巨噬细胞是抗菌防御第一线的多种细胞类型。只有有限数量的主要小鼠模型可用于研究其功能。寿命有限的骨髓源性、巨噬细胞-CSF诱导的细胞是最常见的来源。我们在这里报告一个简单的方法产生自我更新,非转化,GM-CSF/信号转导和转录激活因子5依赖性巨噬细胞(马克斯普朗克研究所细胞)从小鼠胎肝,这反映了先天性免疫特性的肺泡巨噬细胞。马克斯·普朗克研究所细胞对选定的微生物试剂非常敏感,包括细菌LPS、脂肽、结核分枝杆菌、脐带因子和腺病毒,并产生高度促炎性但无抗炎性IL-10应答。它们显示出在其他单核吞噬细胞中尚未观察到的独特的先天反应模式。这包括不同的LPS传感和LPS暴露后IL-1 α产生的前所未有的调节,这可能在体内肺部炎症中起关键作用。总之,马克斯普朗克研究所的细胞为研究巨噬细胞生物学和生物医学科学提供了一个有用的工具。
Macrophages are diverse cell types in the first line of antimicrobial defense. Only a limited number of primary mouse models exist to study their function. Bone marrow-derived, macrophage-CSF-induced cells with a limited life span are the most common source. We report here a simple method yielding self-renewing, nontransformed, GM-CSF/signal transducer and activator of transcription 5-dependent macrophages (Max Planck Institute cells) from mouse fetal liver, which reflect the innate immune characteristics of alveolar macrophages. Max Planck Institute cells are exquisitely sensitive to selected microbial agents, including bacterial LPS, lipopeptide, Mycobacterium tuberculosis, cord factor, and adenovirus and mount highly proinflammatory but no anti-inflammatory IL-10 responses. They show a unique pattern of innate responses not yet observed in other mononuclear phagocytes. This includes differential LPS sensing and an unprecedented regulation of IL-1 alpha production upon LPS exposure, which likely plays a key role in lung inflammation in vivo. In conclusion, Max Planck Institute cells offer an useful tool to study macrophage biology and for biomedical science.