Host DNases prevent vascular occlusion by neutrophil extracellular traps
Host DNases prevent vascular occlusion by neutrophil extracellular traps
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DOI：
10.1126/science.aam8897
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发表时间：
2017-12-01
期刊：
影响因子：
56.9
通讯作者：
Fuchs, Tobias A.
中科院分区：
文献类型：
--
作者：
Jimenez-Alcazar, Miguel;Rangaswamy, Chandini;Fuchs, Tobias A.
血小板和纤维蛋白凝块在止血和血栓形成中阻塞血管。在这里，我们报告了一个非经典的机制，血管闭塞的基础上，中性粒细胞胞外陷阱（NET），DNA纤维释放的中性粒细胞在炎症。我们研究了哪些宿主因素控制NET在体内，发现两种脱氧核糖核酸酶（DNase），DNase 1和DNase 1样3，降解NET在循环中无菌嗜热菌和败血症。在缺乏这两种DNA酶的情况下，血管内NET形成阻塞血管并导致器官损伤的凝块。严重细菌感染患者的血管闭塞与体外降解NET的缺陷和血管内NET凝块的形成有关。DNase 1和DNase 1-like 3独立表达，因此提供双重宿主保护以对抗血管内NET的有害作用。
Platelet and fibrin clots occlude blood vessels in hemostasis and thrombosis. Here we report a noncanonical mechanism for vascular occlusion based on neutrophil extracellular traps (NETs), DNA fibers released by neutrophils during inflammation. We investigated which host factors control NETs in vivo and found that two deoxyribonucleases (DNases), DNase1 and DNase1-like 3, degraded NETs in circulation during sterile neutrophilia and septicemia. In the absence of both DNases, intravascular NETs formed clots that obstructed blood vessels and caused organ damage. Vascular occlusions in patients with severe bacterial infections were associated with a defect to degrade NETs ex vivo and the formation of intravascular NET clots. DNase1 and DNase1-like 3 are independently expressed and thus provide dual host protection against deleterious effects of intravascular NETs.