Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA; Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Aug;1866(8):158964. doi: 10.1016/j.bbalip.2021.158964. Epub 2021 May 10.
Macrophages are almost everywhere in the body, where they serve pivotal functions in maintaining tissue homeostasis, remodeling, and immunoregulation. Macrophages are traditionally thought to differentiate from bone marrow-derived hematopoietic stem cells (HSCs). Emerging studies suggest that some tissue macrophages at steady state originate from embryonic precursors in the yolk sac or fetal liver and are maintained in situ by self-renewal, but bone marrow-derived monocytes can give rise to tissue macrophages in pathogenic settings, such as inflammatory injuries and cancer. Macrophages are popularly classified as Th1 cytokine (e.g. IFNγ)-activated M1 macrophages (the classical activation) or Th2 cytokine (e.g. IL-4)-activated M2 macrophages (the alternative activation). However, given the myriad arrays of stimuli macrophages may encounter from local environment, macrophages exhibit notorious heterogeneity in their phenotypes and functions. Determining the underlying metabolic pathways engaged during macrophage activation is critical for understanding macrophage phenotypic and functional adaptivity under different disease settings. Fatty acid binding proteins (FABPs) represent a family of evolutionarily conserved proteins facilitating lipid transport, metabolism and responses inside cells. More specifically, adipose-FABP (A-FABP) and epidermal-FABP (E-FABP) are highly expressed in macrophages and play a central role in integrating metabolic and inflammatory pathways. In this review we highlight how A-FABP and E-FABP are respectively upregulated in different subsets of activated macrophages and provide a unique perspective in defining macrophage phenotypic and functional heterogeneity through FABP-regulated lipid metabolic and inflammatory pathways.
巨噬细胞几乎存在于身体的各个部位，在维持组织内稳态、重塑和免疫调节中发挥着关键作用。传统上认为巨噬细胞来源于骨髓来源的造血干细胞（HSCs）。新兴的研究表明，一些稳态组织巨噬细胞来源于卵黄囊或胎肝中的胚胎前体，并通过自我更新在原位维持，但骨髓来源的单核细胞可以在炎症损伤和癌症等病理状态下产生组织巨噬细胞。巨噬细胞通常被分为 Th1 细胞因子（如 IFNγ）激活的 M1 巨噬细胞（经典激活）或 Th2 细胞因子（如 IL-4）激活的 M2 巨噬细胞（替代激活）。然而，鉴于巨噬细胞可能从局部环境中遇到的各种刺激，其表型和功能表现出明显的异质性。确定巨噬细胞激活过程中涉及的潜在代谢途径对于理解不同疾病状态下巨噬细胞的表型和功能适应性至关重要。脂肪酸结合蛋白（FABPs）代表一组进化上保守的蛋白质，促进细胞内脂质的运输、代谢和反应。更具体地说，脂肪组织-FABP（A-FABP）和表皮-FABP（E-FABP）在巨噬细胞中高度表达，在整合代谢和炎症途径方面发挥着核心作用。在这篇综述中，我们强调了 A-FABP 和 E-FABP 如何分别在上调不同激活巨噬细胞亚群中发挥作用，并通过 FABP 调节的脂质代谢和炎症途径提供了一个独特的视角来定义巨噬细胞的表型和功能异质性。
