Schuermans Sara, Kestens Caine, Marques Pedro Elias
Laboratory of Molecular Immunology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Cell Death Dis. 2024 Aug 1;15(8):557. doi: 10.1038/s41419-024-06947-5.
Necrosis is an overarching term that describes cell death modalities caused by (extreme) adverse conditions in which cells lose structural integrity. A guaranteed consequence of necrosis is the production of necrotic cell remnants, or debris. Necrotic cell debris is a strong trigger of inflammation, and although inflammatory responses are required for tissue healing, necrotic debris may lead to uncontrolled immune responses and collateral damage. Besides local phagocytosis by recruited leukocytes, there is accumulating evidence that extracellular mechanisms are also involved in necrotic debris clearance. In this review, we focused on systemic clearance mechanisms present in the bloodstream and vasculature that often cooperate to drive the clearance of cell debris. We reviewed the contribution and cooperation of extracellular DNases, the actin-scavenger system, the fibrinolytic system and reticuloendothelial cells in performing clearance of necrotic debris. Moreover, associations of the (mis)functioning of these clearance systems with a variety of diseases were provided, illustrating the importance of the mechanisms of clearance of dead cells in the organism.
坏死是一个总体术语，用于描述由（极端）不利条件导致的细胞死亡方式，在此过程中细胞失去结构完整性。坏死的一个必然结果是产生坏死细胞残余物或碎片。坏死细胞碎片是炎症的强烈触发因素，虽然炎症反应是组织愈合所必需的，但坏死碎片可能导致不受控制的免疫反应和附带损害。除了募集的白细胞进行局部吞噬作用外，越来越多的证据表明细胞外机制也参与坏死碎片的清除。在本综述中，我们重点关注存在于血液和血管系统中的全身清除机制，这些机制通常协同作用以推动细胞碎片的清除。我们回顾了细胞外脱氧核糖核酸酶、肌动蛋白清除系统、纤维蛋白溶解系统和网状内皮细胞在清除坏死碎片中的作用及协同作用。此外，还介绍了这些清除系统（功能异常）与多种疾病的关联，说明了死细胞清除机制在生物体内的重要性。
