Abstract

Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

摘要

代谢产物乳酸一直被视为代谢副产物而非生物活性分子。最近，这种观点发生了变化，因为人们发现乳酸可以作为信号分子，在细胞内和细胞外都具有新颖的信号转导功能，可以调节免疫系统中的关键功能。近年来，越来越多的证据表明乳酸与巨噬细胞的代谢和极化密切相关。在炎症过程中，乳酸是巨噬细胞代谢的调节剂，可以防止过度的炎症反应；在恶性肿瘤中，肿瘤组织产生的乳酸促进肿瘤相关巨噬细胞的极化，进而促进肿瘤进展。在本次审查中，我们检查了乳酸和巨噬细胞代谢之间的关系。我们进一步讨论了乳酸如何在维持巨噬细胞的稳态中发挥作用，以及巨噬细胞极化的生物学和人类疾病中的 M1/M2 失衡。还将讨论靶向乳酸治疗炎症和癌症的潜在方法，以提供治疗疾病的新策略。