Extracellular DNA traps promote thrombosis
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Extracellular DNA traps promote thrombosis. / Fuchs, Tobias A; Brill, Alexander; Duerschmied, Daniel; Schatzberg, Daphne; Monestier, Marc; Myers, Daniel D; Wrobleski, Shirley K; Wakefield, Thomas W; Hartwig, John H; Wagner, Denisa D.
in: P NATL ACAD SCI USA, Jahrgang 107, Nr. 36, 07.09.2010, S. 15880-5.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Extracellular DNA traps promote thrombosis
AU - Fuchs, Tobias A
AU - Brill, Alexander
AU - Duerschmied, Daniel
AU - Schatzberg, Daphne
AU - Monestier, Marc
AU - Myers, Daniel D
AU - Wrobleski, Shirley K
AU - Wakefield, Thomas W
AU - Hartwig, John H
AU - Wagner, Denisa D
PY - 2010/9/7
Y1 - 2010/9/7
N2 - Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.
AB - Neutrophil extracellular traps (NETs) are part of the innate immune response to infections. NETs are a meshwork of DNA fibers comprising histones and antimicrobial proteins. Microbes are immobilized in NETs and encounter a locally high and lethal concentration of effector proteins. Recent studies show that NETs are formed inside the vasculature in infections and noninfectious diseases. Here we report that NETs provide a heretofore unrecognized scaffold and stimulus for thrombus formation. NETs perfused with blood caused platelet adhesion, activation, and aggregation. DNase or the anticoagulant heparin dismantled the NET scaffold and prevented thrombus formation. Stimulation of platelets with purified histones was sufficient for aggregation. NETs recruited red blood cells, promoted fibrin deposition, and induced a red thrombus, such as that found in veins. Markers of extracellular DNA traps were detected in a thrombus and plasma of baboons subjected to deep vein thrombosis, an example of inflammation-enhanced thrombosis. Our observations indicate that NETs are a previously unrecognized link between inflammation and thrombosis and may further explain the epidemiological association of infection with thrombosis.
KW - Animals
KW - DNA
KW - Humans
KW - Thrombosis
U2 - 10.1073/pnas.1005743107
DO - 10.1073/pnas.1005743107
M3 - SCORING: Journal article
C2 - 20798043
VL - 107
SP - 15880
EP - 15885
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 36
ER -