Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage
Resident Macrophages Cloak Tissue Microlesions to Prevent Neutrophil-Driven Inflammatory Damage
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DOI：
10.1016/j.cell.2019.02.028
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发表时间：
2019-04-18
期刊：
影响因子：
64.5
通讯作者：
Germain, Ronald N.
中科院分区：
文献类型：
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作者：
Uderhardt, Stefan;Martins, Andrew J.;Germain, Ronald N.
中性粒细胞被吸引到不同组织中的细胞损伤部位并在其处产生密集群，通常会延长由初始损伤产生的器官结构的局部破坏。由中性粒细胞聚集引起的炎性损伤是否是实质细胞死亡的不可避免的后果尚未探讨。使用动态活体成像和共聚焦多重显微镜的组合，我们在这里报告，组织驻留的巨噬细胞迅速感知单个细胞的死亡，并延长隔离损伤的膜过程，这一过程阻止了导致中性粒细胞群的前馈化学引诱物信号级联的启动。通过这种“伪装”机制，驻留的巨噬细胞防止嗜中性粒细胞介导的炎性损伤，在面对由于机械和其他应力而在许多器官中定期发生的局部细胞损伤时维持组织稳态。
Neutrophils are attracted to and generate dense swarms at sites of cell damage in diverse tissues, often extending the local disruption of organ architecture produced by the initial insult. Whether the inflammatory damage resulting from such neutrophil accumulation is an inescapable consequence of parenchymal cell death has not been explored. Using a combination of dynamic intravital imaging and confocal multiplex microscopy, we report here that tissue-resident macrophages rapidly sense the death of individual cells and extend membrane processes that sequester the damage, a process that prevents initiation of the feedforward chemoattractant signaling cascade that results in neutrophil swarms. Through this "cloaking" mechanism, the resident macrophages prevent neutrophil-mediated inflammatory damage, maintaining tissue homeostasis in the face of local cell injury that occurs on a regular basis in many organs because of mechanical and other stresses.