Morales-Nebreda Luisa, Misharin Alexander V, Perlman Harris, Budinger G R Scott
Dept of Medicine, Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Dept of Medicine, Division of Rheumatology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
Eur Respir Rev. 2015 Sep;24(137):505-9. doi: 10.1183/16000617.0031-2015.
Alveolar macrophages are specialised resident phagocytes in the alveolus, constituting the first line of immune cellular defence in the lung. As the lung microenvironment is challenged and remodelled by inhaled pathogens and air particles, so is the alveolar macrophage pool altered by signals that maintain and/or replace its composition. The signals that induce the recruitment of circulating monocytes to the injured lung, as well as their distinct gene expression profile and susceptibility to epigenetic reprogramming by the local environment remain unclear. In this review, we summarise the unique characteristics of the alveolar macrophage pool ontogeny, phenotypic heterogeneity and plasticity during homeostasis, tissue injury and normal ageing. We also discuss new evidence arising from recent studies where investigators described how the epigenetic landscape drives the specific gene expression profile of alveolar macrophages. Altogether, new analysis of macrophages by means of "omic" technologies will allow us to identify key pathways by which these cells contribute to the development and resolution of lung disease in both mice and humans.
肺泡巨噬细胞是肺泡中特化的常驻吞噬细胞，构成肺部免疫细胞防御的第一道防线。随着肺部微环境受到吸入病原体和空气颗粒的挑战与重塑，肺泡巨噬细胞池也会因维持和/或改变其组成的信号而发生改变。诱导循环单核细胞募集至损伤肺部的信号，以及它们独特的基因表达谱和对局部环境表观遗传重编程的敏感性仍不清楚。在本综述中，我们总结了肺泡巨噬细胞池在稳态、组织损伤和正常衰老过程中的独特特征，包括个体发生、表型异质性和可塑性。我们还讨论了近期研究产生的新证据，其中研究人员描述了表观遗传格局如何驱动肺泡巨噬细胞的特定基因表达谱。总之，通过“组学”技术对巨噬细胞进行新的分析，将使我们能够识别这些细胞在小鼠和人类肺部疾病发生和消退过程中发挥作用的关键途径。
