GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1
GM-CSF regulates alveolar macrophage differentiation and innate immunity in the lung through PU.1
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DOI：
10.1016/s1074-7613(01)00218-7
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发表时间：
2001-10-01
期刊：
影响因子：
32.4
通讯作者：
Trapnell, BC
中科院分区：
文献类型：
--
作者：
Shibata, Y;Berclaz, PY;Trapnell, BC
GM-CSF基因靶向（GM（-/-））小鼠易患呼吸道感染，并分别由于先天免疫功能缺陷和肺泡巨噬细胞（AM）中的表面活性剂催化剂而发生肺泡蛋白沉积症。在GM（-/-）小鼠AM中观察到细胞粘附、吞噬作用、病原体杀伤、甘露糖和Toll样受体表达以及LPS或肽聚糖刺激的TNF α释放减少。在GM（-/-）转基因小鼠AM中，PU.1转录因子的表达明显降低，而在SPC GM/GM（-/-）转基因小鼠肺中，选择性表达GM-CSF可使PU.1转录因子的表达恢复。逆转录病毒介导的PU.1在GM（-/-）小鼠AM中的表达挽救了AM的宿主防御功能和表面活性剂催化。我们的结论是，PU.1介导GM-CSF依赖性的影响，终末分化的AM调节先天免疫功能和表面活性剂catastrophic AM。
GM-CSF gene targeted (GM(-/-)) mice are susceptible to respiratory infections and develop alveolar proteinosis due to defects in innate immune function and surfactant catabolism in alveolar macrophages (AMs), respectively. Reduced cell adhesion, phagocytosis, pathogen killing, mannose- and Toll-like receptor expression, and LPS- or peptidoglycan-stimulated TNF alpha, release were observed in AMs from GM(-/-) mice. The transcription factor PU.1 was markedly reduced in AMs of GM(-/-) mice in vivo and was restored by selective expression of GM-CSF in the lungs of SPC-GM/GM(-/-) transgenic mice. Retrovirus-mediated expression of PU.1 in AMs from GM(-/-) mice rescued host defense functions and surfactant catabolism by AMs. We conclude that PU.1 mediates GM-CSF-dependent effects on terminal differentiation of AMs regulating innate immune functions and surfactant catabolism by AMs.