| Literature DB >> 29191910 |
Miguel Jiménez-Alcázar1, Chandini Rangaswamy1, Rachita Panda1, Josephine Bitterling1, Yashin J Simsek1, Andy T Long1, Rostyslav Bilyy2, Veit Krenn3, Christoph Renné4, Thomas Renné1,5, Stefan Kluge6, Ulf Panzer7, Ryushin Mizuta8, Hans Georg Mannherz9, Daisuke Kitamura8, Martin Herrmann10, Markus Napirei9, Tobias A Fuchs11,5.
Abstract
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.Entities:
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Year: 2017 PMID： 29191910 DOI： 10.1126/science.aam8897
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728