Abstract：
In an adult human, billions of cells die and turn over daily. During this process, many apoptotic cells are produced and subsequently cleared by phagocytes - a process termed efferocytosis, which plays a critical role in tissue homeostasis. Efferocytosis is an important mechanism in the control of inflammatory processes. Efficient efferocytosis inhibits accumulation of apoptotic cells/debris and maintains homeostasis before the onset of necrosis (secondary necrosis), which promotes inflammation or injury. During efferocytosis, mitochondrial fission and the oxidative stress process are linked through reactive oxygen species production and oxidative stress control. Autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis by activated inflammatory cells, particularly neutrophils and macrophages. Autophagy in neutrophils is activated by phagocytosis of pathogens or activation of pattern recognition receptors. Autophagy is essential for major neutrophil functions, including degranulation, reactive oxygen species production, oxidative stress and release of neutrophil extracellular cytokines. Failed efferocytosis is a key mechanism driving the development and progression of chronic inflammatory diseases, including atherosclerosis, cardiometabolic pathology, neurodegenerative disease and cancer. Impairment of efferocytosis in apoptotic macrophages is a determinant of atherosclerosis severity and the vulnerability of plaques to rupture. Recent results suggest that inhibition of efferocytosis in the protection of the myocardium results in reduced infiltration of reparatory macrophages into the tissue, in association with oxidative stress reduction. Activated macrophages play a central role in the development and resolution of inflammation. The resolution of inflammation through efferocytosis is an endogenous process that protects host tissues from prolonged or excessive inflammation. Accordingly, therapeutic strategies that ameliorate efferocytosis control would be predicted to dampen inflammation and improve resolution. Thus, therapies targeting efferocytosis will provide a new means of treating and preventing cardiovascular and metabolic diseases involving the chronic inflammatory state.
摘要：
在一个成年人身上，每天都有数十亿个细胞死亡和翻转。在这个过程中,许多凋亡细胞产生并随后被吞噬细胞清除——这一过程被称为Effercytosis，在组织稳态中起着关键作用。在控制炎症过程中,胞质增生是一种重要的机制。有效的细胞凋亡抑制凋亡细胞/碎片的积累，并在坏死（继发性坏死）开始之前维持体内平衡。促进炎症或损伤。在红细胞增多期间，线粒体裂变和氧化应激过程是通过活性氧的产生和氧化应激控制联系在一起的。自噬在抑制炎症和凋亡中起重要作用,并通过激活的炎症细胞促进细胞增生，特别是中性粒细胞和巨噬细胞。嗜中性粒细胞中的自噬通过病原体的吞噬作用或模式识别受体的激活而被激活。自噬对主要的中性粒细胞功能至关重要，包括脱粒,活性氧的产生，氧化应激和中性粒细胞细胞外细胞因子的释放。失败的有效细胞增殖是驱动慢性炎症性疾病发展的关键机制。包括动脉粥样硬化,心脏代谢病理学，神经退行性疾病和癌症。凋亡巨噬细胞中的有效细胞功能受损是动脉粥样硬化严重程度和斑块破裂脆弱性的决定因素。最近的结果表明，抑制心肌保护中的有效细胞作用会导致补充巨噬细胞向组织的浸润减少，与氧化应激减少有关。活化的巨噬细胞在炎症的发展和解决中起着核心作用。通过细胞增生解决炎症是保护宿主组织免受长期或过度炎症的内源性过程。因此，可以预测改善有效细胞增多控制的治疗策略可以抑制炎症并提高消退率.因此，靶向治疗将为治疗和预防涉及慢性炎症状态的心血管和代谢性疾病提供新的手段。
