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-γ) 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-γ) 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-γ) macrophages, depending on the glycolytic metabolism to support their profile and functions.

中文翻译：

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有氧糖酵解是维持肿瘤相关巨噬细胞的M2样极化的代谢要求。

巨噬细胞（MO）是多功能细胞，根据激活刺激和微环境的不同，表现出不同的功能表型。巨噬细胞的差异激活受到细胞内新陈代谢的深刻变化的支持，M1 / M（LPS +IFN-γ）表型依赖于有氧糖酵解，而M2 / M（IL-4）巨噬细胞则依赖于氧化代谢，这已被广泛接受。另一方面，尽管肿瘤相关巨噬细胞（TAM）以M2 / M（IL-4）标记的高表达为特征，但目前尚不清楚TAM是否呈现出与M2 / M（IL-4）相同的氧化代谢谱细胞。在这里，我们首次证明，尽管它们高表达M2 / M（IL-4）标记，但TAM仍显示出高糖酵解活性，并具有类似于M1 / M（LPS +IFN-γ）表型的高乳酸分泌。该活性似乎对TAM的M2谱至关重要，因为抑制了糖酵解作用，而不是氧化磷酸化或戊糖磷酸途径的损伤，却减少了M2 / M（IL-4）标记的表达。这些新数据表明，TAM尽管通常表型为M2 / M（IL-4）样巨噬细胞，但它们在代谢上不同于这些细胞，与M1 / M（LPS +IFN-γ）巨噬细胞非常相似，具体取决于糖酵解代谢以支持其特性和功能。