Aerobic glycolysis is a metabolic requirement to maintain the M2-like polarization of tumor-associated macrophages
Aerobic glycolysis is a metabolic requirement to maintain the M2-like polarization of tumor-associated macrophages
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DOI：
10.1016/j.bbamcr.2019.118604
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发表时间：
2020-02-01
影响因子：
5.1
通讯作者：
Barja-Fidalgo, Christina
中科院分区：
文献类型：
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作者：
de-Brito, Natalia M.;Duncan-Moretti, Julia;Barja-Fidalgo, Christina
巨噬细胞（MO）是多功能细胞，根据激活刺激和微环境呈现不同的功能表型。巨噬细胞的差异活化得到了细胞内代谢变化的支持，公认M1/M（LPS + IFN-γ）表型依赖于有氧糖酵解，而M2/M（IL-4）巨噬细胞依赖于氧化代谢。另一方面，尽管肿瘤相关巨噬细胞（TAM）的特征在于其M2/M（IL-4）标志物的高表达，但目前尚不清楚TAM是否呈现与M2/M（IL-4）细胞相同的氧化代谢谱。在此，我们首次证明，尽管TAM高表达M2/M（IL-4）标记物，但TAM显示高糖酵解活性，具有类似于M1/M（LPS + IFN-γ）表型的高乳酸分泌。这种活性似乎对TAM的M2谱是必不可少的，因为糖酵解的抑制，而不是氧化磷酸化或戊糖磷酸途径的损害，减少了M2/M（IL-4）标志物的表达。这些新的数据表明，TAM虽然通常表型为M2/M（IL-4）样巨噬细胞，但它们在代谢上与这些细胞不同，与M1/M（LPS + IFN-γ）巨噬细胞相当相似，这取决于糖酵解代谢以支持它们的特征和功能。
Macrophages (MO) are versatile cells, assuming distinct functional phenotypes depending on the activating stimulus and the microenvironment. The differential activation of macrophages is supported by profound intracellular metabolic changes, being well accepted that the M1/M(LPS + IFN-gamma) phenotype rely on aerobic glycolysis, while M2/M(IL-4) macrophages depend on oxidative metabolism. On the other hand, although tumor-associated macrophages (TAMs) are characterized by their high expression of M2/M(IL-4) markers, is currently unclear whether TAMs present the same oxidative metabolic profile of M2/M(IL-4) cells. Herein, we demonstrate for the first time that despite their high expression of M2/M(IL-4) markers, TAMs show high glycolytic activity, with high lactate secretion similar to the M1/M(LPS + IFN-gamma) phenotype. This activity seems to be essential for the M2 profile of TAMs, since the inhibition of glycolysis, but not the impairment of the oxidative phosphorylation or pentose phosphate pathway, diminished the expression of M2/M(IL-4) markers. These novel data indicate that TAMs, although are usually phenotyped as M2/M(IL-4)-like macrophages, they are metabolically distinct from these cells, being rather similar to M1/M(LPS + IFN-gamma) macrophages, depending on the glycolytic metabolism to support their profile and functions.