糖酵解产物乳酸对M2-肿瘤相关巨噬细胞亚群重塑作用的研究

目的:研究糖酵解产物乳酸对巨噬细胞表型极化的影响。方法:我们选取人单核/巨噬细胞系THP-1，乳酸处理后采用RT-PCR、Western blot、免疫荧光染色激光共聚焦、ELISA等手段，观察指标:CD68、CD163变化；分泌因子:TNF-α、IFN-γ、IL-12、IL-10 变化。结果:15 mmol/L浓度的乳酸可显著上调巨噬细胞M2型标志分子CD163的表达(P＜0.05)，上调M2-TAM分泌因子IFN-γ和IL-10的表达(P＜0.05)，下调M1-TAM分泌因子TNF-α和IL-12的表达(P＜0.05)。结论:乳酸可重塑巨噬细胞向M2-TAM亚群分布，揭示肿瘤细胞糖酵解产生乳酸可能通过重塑巨噬细胞表型发挥重要的促瘤作用。

Effect of lactic acid on reshaping of M2-TAM subsets

Objective:To study the effects of lactic acid on phenotypic polarization of macrophages.Methods:The human monocyte/macrophage cell line THP-1 was selected and treated with lactic acid.Immunofluorescence staining,laser confocal microscopy,RT-PCR,Western blot,and ELISA methods were used to observe changes in CD68,CD163 and the cytokine TNF-α,IFN-γ,IL-12,IL-10.Results:Lactic acid at a concentration of 15 mmol/L significantly up-regulated the expression of the M2-macrophage marker CD163(P＜0.05),up-regulated the expression of the cytokines IFN-γ and IL-10 secreted by M2-TAM (P＜0.05),down-regulated the expression of the cytokines TNF-α and IL-12 secreted by M1-TAM (P＜0.05).Conclusion:Lactic acid can reshape the distribution of M2-TAM subsets to assist tumor immune escape,revealing that macrophages,as "checkpoints" in organisms,are bridges connecting immune state and tumor evolution,and can be used as a target in tumor treatment.