Division of Immunology, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States.
Division of Gastroenterology, Harvard Medical School, Boston Children's Hospital, Boston, MA, United States.
Front Endocrinol (Lausanne). 2021 Mar 15;12:626842. doi: 10.3389/fendo.2021.626842. eCollection 2021.
Endogenous oxidized phospholipids are produced during tissue stress and are responsible for sustaining inflammatory responses in immune as well as non-immune cells. Their local and systemic production and accumulation is associated with the etiology and progression of several inflammatory diseases, but the molecular mechanisms that underlie the biological activities of these oxidized phospholipids remain elusive. Increasing evidence highlights the ability of these stress mediators to modulate cellular metabolism and pro-inflammatory signaling in phagocytes, such as macrophages and dendritic cells, and to alter the activation and polarization of these cells. Because these immune cells serve a key role in maintaining tissue homeostasis and organ function, understanding how endogenous oxidized lipids reshape phagocyte biology and function is vital for designing clinical tools and interventions for preventing, slowing down, or resolving chronic inflammatory disorders that are driven by phagocyte dysfunction. Here, we discuss the metabolic and signaling processes elicited by endogenous oxidized lipids and outline new hypotheses and models to elucidate the impact of these lipids on phagocytes and inflammation.
内源性氧化磷脂在组织应激时产生，负责维持免疫细胞和非免疫细胞的炎症反应。它们在局部和全身的产生和积累与几种炎症性疾病的病因和进展有关，但这些氧化磷脂的生物学活性的分子机制仍不清楚。越来越多的证据强调了这些应激介质调节吞噬细胞（如巨噬细胞和树突状细胞）中细胞代谢和促炎信号的能力，并改变这些细胞的激活和极化。由于这些免疫细胞在维持组织内稳态和器官功能方面起着关键作用，因此了解内源性氧化脂质如何重塑吞噬细胞的生物学和功能对于设计预防、减缓或解决由吞噬细胞功能障碍驱动的慢性炎症性疾病的临床工具和干预措施至关重要。在这里，我们讨论了内源性氧化脂质引起的代谢和信号过程，并概述了新的假设和模型，以阐明这些脂质对吞噬细胞和炎症的影响。
