Department of Molecular Pharmacology and Physiology, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Department of Surgery, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Immunol Lett. 2023 Feb;254:41-53. doi: 10.1016/j.imlet.2023.02.001. Epub 2023 Feb 4.
The phagocytosis and clearance of dying cells by macrophages, a process termed efferocytosis, is essential for both maintaining homeostasis and promoting tissue repair after infection or sterile injury. If not removed in a timely manner, uncleared cells can undergo secondary necrosis, and necrotic cells lose membrane integrity, release toxic intracellular components, and potentially induce inflammation or autoimmune diseases. Efferocytosis also initiates the repair process by producing a wide range of pro-reparative factors. Accumulating evidence has revealed that macrophage efferocytosis defects are involved in the development and progression of a variety of inflammatory and autoimmune diseases. The underlying mechanisms of efferocytosis impairment are complex, disease-dependent, and incompletely understood. In this review, we will first summarize the current knowledge about the normal signaling and metabolic processes of macrophage efferocytosis and its importance in maintaining tissue homeostasis and repair. We then will focus on analyzing the molecular and cellular mechanisms underlying efferocytotic abnormality (impairment) in disease or injury conditions. Next, we will discuss the potential molecular targets for enhanced efferocytosis in animal models of disease. To provide a balanced view, we will also discuss some deleterious effects of efferocytosis.
巨噬细胞吞噬和清除死亡细胞的过程，即噬作用，对于维持内环境平衡和感染或无菌损伤后组织修复至关重要。如果不能及时清除，未清除的细胞可能会发生继发性坏死，而坏死细胞会失去膜的完整性，释放有毒的细胞内成分，并可能引发炎症或自身免疫性疾病。噬作用还通过产生广泛的促修复因子来启动修复过程。越来越多的证据表明，巨噬细胞噬作用缺陷与多种炎症和自身免疫性疾病的发生和发展有关。噬作用受损的潜在机制复杂，依赖于疾病且尚未完全阐明。在这篇综述中，我们将首先总结巨噬细胞噬作用的正常信号和代谢过程及其在维持组织内环境平衡和修复中的重要性。然后，我们将重点分析疾病或损伤状态下噬作用异常（损伤）的分子和细胞机制。接下来，我们将讨论在疾病动物模型中增强噬作用的潜在分子靶点。为了提供平衡的观点，我们还将讨论噬作用的一些有害影响。
