Laboratory of Molecular Mechanisms of Therapy of Diseases, Institute of Internal Medicine, Siberian Branch of the Russian Academy of Medical Sciences, ul. Bogatkova 175/1, 630089 Novosibirsk, Russia.
Biochemistry (Mosc). 2012 Apr;77(4):327-38. doi: 10.1134/S0006297912040025.
Transformation of macrophages into foam cells is traditionally considered in the context of atherogenesis, because lipid accumulation is believed to be a consequence of uptake of oxidized low density lipoproteins (oxLDL) through scavenger receptors (SR) of macrophages. However, an excessive uptake of oxLDL is recently shown to trigger compensatory mechanisms of cholesterol elimination from macrophages. Maintaining the lipid homeostasis in macrophages is mediated by regulation of a system of lipid sensors, which is reprogrammed under conditions of inflammation leading to formation of foam cell phenotype without involvement of SR. The increase in the inflammatory potential on macrophage polarization into the M1 phenotype is associated with suppression of LXR and PPAR, their target genes, induction of expression of genes responsible for fatty acid and cholesterol metabolism controlled by SREBP1c and SREBP2, proteins associated with lipid inclusions, macropinocytosis activation, secretion of LXR and PPAR endogenous ligands, and development of apoptosis. In this review the role of foam cells in development and resolution of acute inflammation, mechanisms of their formation from macrophages infected by some bacterial and virus pathogens causing chronic inflammation, and the significance of LXR and PPAR as therapeutic targets in chronic infectious and inflammatory diseases are also discussed.
巨噬细胞向泡沫细胞的转化在动脉粥样硬化形成的背景下被认为是传统的，因为脂质的积累被认为是巨噬细胞通过清道夫受体 (SR) 摄取氧化的低密度脂蛋白 (oxLDL) 的结果。然而，最近的研究表明，oxLDL 的过度摄取会触发胆固醇从巨噬细胞中消除的代偿机制。在炎症条件下，维持巨噬细胞中脂质稳态是通过调节脂质传感器系统来介导的，这会导致泡沫细胞表型的形成，而不涉及 SR。巨噬细胞向 M1 表型极化时炎症潜力的增加与 LXR 和 PPAR 的抑制有关，它们的靶基因，诱导控制由 SREBP1c 和 SREBP2 控制的脂肪酸和胆固醇代谢的基因的表达，与脂质包含物、巨胞饮激活、LXR 和 PPAR 内源性配体的分泌以及细胞凋亡的发展有关。在这篇综述中，还讨论了泡沫细胞在急性炎症的发展和消退中的作用、它们在由引起慢性炎症的某些细菌和病毒病原体感染的巨噬细胞中形成的机制，以及 LXR 和 PPAR 作为慢性感染性和炎症性疾病的治疗靶点的意义。
