谷氨酰胺、乳酸和甘油的糖生成和糖异生支持人类巨噬细胞的功能。
Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.
发表日期：2024 Oct 18
作者：
Najia Jeroundi, Charlotte Roy, Laetitia Basset, Pascale Pignon, Laurence Preisser, Simon Blanchard, Cinzia Bocca, Cyril Abadie, Julie Lalande, Naïg Gueguen, Guillaume Mabilleau, Guy Lenaers, Aurélie Moreau, Marie-Christine Copin, Guillaume Tcherkez, Yves Delneste, Dominique Couez, Pascale Jeannin
来源：
EMBO REPORTS
摘要：
巨噬细胞抵抗感染并确保组织修复，通常在营养不良的伤口部位发挥作用。我们研究了人类巨噬细胞代谢糖原的能力。我们观察到细胞因子 GM-CSF 和 M-CSF 加上 IL-4 诱导单核细胞来源的巨噬细胞糖原生成和糖原积累。在存在炎症细胞因子 GM-CSF 和 IFNγ（M1 细胞）的情况下培养的细胞中，通过磷酸烯醇丙酮酸羧激酶 2 (PCK2) 和果糖 1,6-二磷酸酶 1 (FBP1) 发生糖异生。药物或基因沉默技术的酶抑制以及 13C 示踪表明，谷氨酰胺（通过 TCA 循环代谢）、乳酸和甘油是仅在 M1 细胞中糖异生的底物。肿瘤相关巨噬细胞（TAM）也储存糖原并可以进行糖异生。最后，无论细胞外葡萄糖的可用性如何，巨噬细胞糖原分解和磷酸戊糖途径（PPP）都支持细胞因子的分泌和吞噬作用。因此，糖原代谢支持人类 M1 和 M2 细胞的功能，炎症性 M1 细胞表现出可能依赖于糖异生。© 2024。作者。
Macrophages fight infection and ensure tissue repair, often operating at nutrient-poor wound sites. We investigated the ability of human macrophages to metabolize glycogen. We observed that the cytokines GM-CSF and M-CSF plus IL-4 induced glycogenesis and the accumulation of glycogen by monocyte-derived macrophages. Glyconeogenesis occurs in cells cultured in the presence of the inflammatory cytokines GM-CSF and IFNγ (M1 cells), via phosphoenolpyruvate carboxykinase 2 (PCK2) and fructose-1,6-bisphosphatase 1 (FBP1). Enzyme inhibition with drugs or gene silencing techniques and 13C-tracing demonstrate that glutamine (metabolized by the TCA cycle), lactic acid, and glycerol were substrates of glyconeogenesis only in M1 cells. Tumor-associated macrophages (TAMs) also store glycogen and can perform glyconeogenesis. Finally, macrophage glycogenolysis and the pentose phosphate pathway (PPP) support cytokine secretion and phagocytosis regardless of the availability of extracellular glucose. Thus, glycogen metabolism supports the functions of human M1 and M2 cells, with inflammatory M1 cells displaying a possible dependence on glyconeogenesis.© 2024. The Author(s).