Orihuela Ruben, McPherson Christopher A, Harry Gaylia Jean
Neurotoxicology Group, National Toxicology Program Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.
Br J Pharmacol. 2016 Feb;173(4):649-65. doi: 10.1111/bph.13139. Epub 2015 May 11.
Microglia are critical nervous system-specific immune cells serving as tissue-resident macrophages influencing brain development, maintenance of the neural environment, response to injury and repair. As influenced by their environment, microglia assume a diversity of phenotypes and retain the capability to shift functions to maintain tissue homeostasis. In comparison with peripheral macrophages, microglia demonstrate similar and unique features with regards to phenotype polarization, allowing for innate immunological functions. Microglia can be stimulated by LPS or IFN-γ to an M1 phenotype for expression of pro-inflammatory cytokines or by IL-4/IL-13 to an M2 phenotype for resolution of inflammation and tissue repair. Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. Studies using peripheral immune cells demonstrate that polarization to an M1 phenotype is often accompanied by a shift in cells from oxidative phosphorylation to aerobic glycolysis for energy production. More recently, the link between polarization and mitochondrial energy metabolism has been considered in microglia. Under these conditions, energy demands would be associated with functional activities and cell survival and thus, may serve to influence the contribution of microglia activation to various neurodegenerative conditions. This review examines the polarization states of microglia and their relationship to mitochondrial metabolism. Additional supporting experimental data are provided to demonstrate mitochondrial metabolic shifts in primary microglia and the BV-2 microglia cell line induced under LPS (M1) and IL-4/IL-13 (M2) polarization.
小胶质细胞是中枢神经系统特有的免疫细胞，作为组织驻留巨噬细胞影响大脑发育、维持神经环境、对损伤作出反应和进行修复。受其所处环境的影响，小胶质细胞呈现出多种表型，并保留了转变功能以维持组织稳态的能力。与外周巨噬细胞相比，小胶质细胞在表型极化方面表现出相似和独特的特征，从而具备先天性免疫功能。小胶质细胞可被脂多糖（LPS）或干扰素-γ刺激为M1表型以表达促炎细胞因子，或被白细胞介素-4/白细胞介素-13刺激为M2表型以促进炎症消退和组织修复。越来越多的证据表明代谢重编程在先天性炎症反应的调节中发挥作用。使用外周免疫细胞的研究表明，向M1表型的极化通常伴随着细胞从氧化磷酸化转变为有氧糖酵解以产生能量。最近，小胶质细胞中极化与线粒体能量代谢之间的联系也受到了关注。在这些情况下，能量需求将与功能活动和细胞存活相关，因此可能影响小胶质细胞激活对各种神经退行性疾病的作用。本综述探讨了小胶质细胞的极化状态及其与线粒体代谢的关系。还提供了额外的支持性实验数据，以证明在LPS（M1）和白细胞介素-4/白细胞介素-13（M2）极化诱导下原代小胶质细胞和BV-2小胶质细胞系中的线粒体代谢变化。
