Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.
Xiangya School of Medicine, Central South University, Changsha, China.
Cell Death Dis. 2022 Apr 16;13(4):355. doi: 10.1038/s41419-022-04775-z.
Ferroptosis, a newly discovered iron-dependent cell death pathway, is characterized by lipid peroxidation and GSH depletion mediated by iron metabolism and is morphologically, biologically and genetically different from other programmed cell deaths. Besides, ferroptosis is usually found accompanied by inflammatory reactions. So far, it has been found participating in the development of many kinds of diseases. Macrophages are a group of immune cells that widely exist in our body for host defense and play an important role in tissue homeostasis by mediating inflammation and regulating iron, lipid and amino acid metabolisms through their unique functions like phagocytosis and efferocytosis, cytokines secretion and ROS production under different polarization. According to these common points in ferroptosis characteristics and macrophages functions, it's obvious that there must be relationship between macrophages and ferroptosis. Therefore, our review aims at revealing the interaction between macrophages and ferroptosis concerning three metabolisms and integrating the application of certain relationship in curing diseases, mostly cancer. Finally, we also provide inspirations for further studies in therapy for some diseases by targeting certain resident macrophages in distinct tissues to regulate ferroptosis. FACTS: Ferroptosis is considered as a newly discovered form characterized by its nonapoptotic and iron-dependent lipid hydroperoxide, concerning iron, lipid and amino acid metabolisms. Ferroptosis has been widely found playing a crucial part in various diseases, including hepatic diseases, neurological diseases, cancer, etc. Macrophages are phagocytic immune cells, widely existing and owning various functions such as phagocytosis and efferocytosis, cytokines secretion and ROS production. Macrophages are proved to participate in mediating metabolisms and initiating immune reactions to maintain balance in our body. Recent studies try to treat cancer by altering macrophages' polarization which damages tumor microenvironment and induces ferroptosis of cancer cells. OPEN QUESTIONS: How do macrophages regulate ferroptosis of other tissue cells specifically? Can we use the interaction between macrophages and ferroptosis in treating diseases other than cancer? What can we do to treat diseases related to ferroptosis by targeting macrophages? Is the use of the relationship between macrophages and ferroptosis more effective than other therapies when treating diseases?
铁死亡是一种新发现的铁依赖性细胞死亡途径,其特征是铁代谢介导的脂质过氧化和 GSH 耗竭,在形态、生物学和遗传学上与其他程序性细胞死亡不同。此外,铁死亡通常伴随着炎症反应。到目前为止,它已被发现参与多种疾病的发展。巨噬细胞是一类广泛存在于体内的免疫细胞,通过吞噬作用和胞外噬作用、细胞因子分泌和 ROS 产生等独特功能,在宿主防御中发挥重要作用,并通过调节炎症和铁、脂质和氨基酸代谢来维持组织内稳态。根据铁死亡特征和巨噬细胞功能的这些共同点,可以明显看出巨噬细胞和铁死亡之间存在一定的关系。因此,我们的综述旨在揭示巨噬细胞与铁死亡之间在三种代谢方面的相互作用,并整合某些关系在治疗疾病,尤其是癌症中的应用。最后,我们还通过针对不同组织中特定的驻留巨噬细胞来调节铁死亡,为某些疾病的治疗提供了进一步研究的启示。
要点:铁死亡被认为是一种新发现的形式,其特征是非凋亡和铁依赖性脂质过氧化物,涉及铁、脂质和氨基酸代谢。铁死亡已广泛发现在各种疾病中起着关键作用,包括肝脏疾病、神经疾病、癌症等。巨噬细胞是吞噬免疫细胞,广泛存在并具有多种功能,如吞噬作用和胞外噬作用、细胞因子分泌和 ROS 产生。研究证明巨噬细胞参与调节代谢和引发免疫反应,以维持体内平衡。最近的研究试图通过改变巨噬细胞的极化来治疗癌症,这种极化破坏肿瘤微环境并诱导癌细胞的铁死亡。
问题:巨噬细胞如何特异性地调节其他组织细胞的铁死亡?我们能否利用巨噬细胞和铁死亡之间的相互作用来治疗癌症以外的疾病?我们可以通过靶向巨噬细胞来治疗与铁死亡相关的疾病吗?在治疗与铁死亡相关的疾病时,靶向巨噬细胞和铁死亡的关系是否比其他疗法更有效?
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