Zent Clive S, Elliott Michael R
Wilmot Cancer Institute, University of Rochester Medical Center, NY, USA.
Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, NY, USA.
FEBS J. 2017 Apr;284(7):1021-1039. doi: 10.1111/febs.13961. Epub 2016 Nov 29.
The phagocytic clearance of host cells is important for eliminating dying cells and for the therapeutic clearance of antibody-targeted cells. As ubiquitous, motile and highly phagocytic immune cells, macrophages are principal players in the phagocytic removal of host cells throughout the body. In recent years, great strides have been made in identifying the molecular mechanisms that control the recognition and phagocytosis of cells by macrophages. However, much less is known about the physical and metabolic constraints that govern the amount of cellular material macrophages can ingest and how these limitations affect the overall efficiency of host cell clearance in health and disease. In this review we will discuss, in the contexts of apoptotic cells and antibody-targeted malignant cells, how physical and metabolic factors associated with the internalization of host cells are relayed to the phagocytic machinery and how these signals can impact the overall efficiency of cell clearance. We also discuss how this information can be leveraged to increase cell clearance for beneficial therapeutic outcomes.
宿主细胞的吞噬清除对于清除垂死细胞以及抗体靶向细胞的治疗性清除非常重要。作为普遍存在、具有运动能力且高度吞噬的免疫细胞，巨噬细胞是全身吞噬清除宿主细胞的主要参与者。近年来，在确定控制巨噬细胞识别和吞噬细胞的分子机制方面取得了巨大进展。然而，对于控制巨噬细胞能够摄取的细胞物质数量的物理和代谢限制以及这些限制如何影响健康和疾病状态下宿主细胞清除的整体效率，人们了解得要少得多。在本综述中，我们将在凋亡细胞和抗体靶向恶性细胞的背景下讨论与宿主细胞内化相关的物理和代谢因素如何传递到吞噬机制，以及这些信号如何影响细胞清除的整体效率。我们还将讨论如何利用这些信息来提高细胞清除率以获得有益的治疗效果。
