Department of Immunology and Oncology, National Center for Biotechnology/The Spanish National Research Council (CSIC), Madrid, Spain.
Biocomputing Unit, National Center for Biotechnology/The Spanish National Research Council (CSIC), Madrid, Spain.
Front Immunol. 2023 Jul 5;14:1200259. doi: 10.3389/fimmu.2023.1200259. eCollection 2023.
Macrophages are a heterogeneous population of innate immune cells that support tissue homeostasis through their involvement in tissue development and repair, and pathogen defense. Emerging data reveal that metabolism may control macrophage polarization and function and, conversely, phenotypic polarization may drive metabolic reprogramming.
Here we use biochemical analysis, correlative cryogenic fluorescence microscopy and cryo-focused ion-beam scanning electron microscopy.
We demonstrate that growth hormone (GH) reprograms inflammatory GM-CSF-primed monocyte-derived macrophages (GM-MØ) by functioning as a metabolic modulator. We found that exogenous treatment of GM-MØ with recombinant human GH reduced glycolysis and lactate production to levels similar to those found in anti-inflammatory M-MØ. Moreover, GH treatment of GM-MØ augmented mitochondrial volume and altered mitochondrial dynamics, including the remodeling of the inner membrane to increase the density of cristae.
Our data demonstrate that GH likely serves a modulatory role in the metabolism of inflammatory macrophages and suggest that metabolic reprogramming of macrophages should be considered as a new target to intervene in inflammatory diseases.
巨噬细胞是一种异质性的先天免疫细胞群体，通过参与组织发育和修复以及病原体防御来支持组织稳态。新出现的数据表明，代谢可能控制巨噬细胞的极化和功能，而表型极化则可能推动代谢重编程。
在这里，我们使用生化分析、相关低温荧光显微镜和低温聚焦离子束扫描电子显微镜。
我们证明，生长激素（GH）作为代谢调节剂重新编程炎性 GM-CSF 激活的单核细胞来源的巨噬细胞（GM-MØ）。我们发现，重组人生长激素对 GM-MØ 的外源性处理降低了糖酵解和乳酸生成，使其水平与抗炎性 M-MØ 相似。此外，GH 处理 GM-MØ 增加了线粒体体积，并改变了线粒体动力学，包括重塑内膜以增加嵴密度。
我们的数据表明，GH 可能在炎性巨噬细胞的代谢中发挥调节作用，并表明巨噬细胞的代谢重编程应被视为干预炎症性疾病的新靶点。
