Host DNases prevent vascular occlusion by neutrophil extracellular traps
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Host DNases prevent vascular occlusion by neutrophil extracellular traps. / Jiménez-Alcázar, Miguel; Rangaswamy, Chandini; Panda, Rachita; Bitterling, Josephine; Simsek, Yashin J; Long, Andy T; Bilyy, Rostyslav; Krenn, Veit; Renné, Christoph; Renné, Thomas; Kluge, Stefan; Panzer, Ulf; Mizuta, Ryushin; Mannherz, Hans Georg; Kitamura, Daisuke; Herrmann, Martin; Napirei, Markus; Fuchs, Tobias A.
in: SCIENCE, Jahrgang 358, Nr. 6367, 01.12.2017, S. 1202-1206.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Host DNases prevent vascular occlusion by neutrophil extracellular traps
AU - Jiménez-Alcázar, Miguel
AU - Rangaswamy, Chandini
AU - Panda, Rachita
AU - Bitterling, Josephine
AU - Simsek, Yashin J
AU - Long, Andy T
AU - Bilyy, Rostyslav
AU - Krenn, Veit
AU - Renné, Christoph
AU - Renné, Thomas
AU - Kluge, Stefan
AU - Panzer, Ulf
AU - Mizuta, Ryushin
AU - Mannherz, Hans Georg
AU - Kitamura, Daisuke
AU - Herrmann, Martin
AU - Napirei, Markus
AU - Fuchs, Tobias A
N1 - Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1126/science.aam8897
DO - 10.1126/science.aam8897
M3 - SCORING: Journal article
C2 - 29191910
VL - 358
SP - 1202
EP - 1206
JO - SCIENCE
JF - SCIENCE
SN - 0036-8075
IS - 6367
ER -