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Host DNases prevent vascular occlusion by neutrophil extracellular traps

by Fuchs, Tobias A. , Long, Andy T. , Herrmann, Martin , Kluge, Stefan , Renné, Thomas , Mizuta, Ryushin , Bilyy, Rostyslav , Krenn, Veit , Napirei, Markus , Panzer, Ulf , Panda, Rachita , Renné, Christoph , Jiménez-Alcázar, Miguel , Rangaswamy, Chandini , Simsek, Yashin J. , Kitamura, Daisuke , Mannherz, Hans Georg , Bitterling, Josephine

in Animals / Bacteria / Bacterial diseases / Blood vessels / Chromatin / Degradation / Deoxyribonuclease I - blood / Deoxyribonuclease I - genetics / Deoxyribonuclease I - metabolism / Deoxyribonucleic acid / DNA / DNA - metabolism / Endodeoxyribonucleases - blood / Endodeoxyribonucleases - genetics / Endodeoxyribonucleases - metabolism / Extracellular Traps - enzymology / Extracellular Traps - genetics / Fibers / Fibrin / Granulocyte Colony-Stimulating Factor - genetics / Granulocyte Colony-Stimulating Factor - metabolism / Hemostasis / Hemostasis - genetics / Hemostasis - physiology / Hemostatic Disorders - enzymology / Hemostatic Disorders - genetics / Hemostatics / Humans / In vivo methods and tests / Inflammation - blood / Inflammation - enzymology / Lattices / Leukocytes (neutrophilic) / Liver - metabolism / Lung - blood supply / Lung - metabolism / Lung - pathology / Mice / Mice, Mutant Strains / Neutrophilia / Neutrophils / Neutrophils - enzymology / Occlusion / Proteins / Rodents / Sepsis / Sepsis - blood / Sepsis - enzymology / Septicemia / Thromboembolism / Thrombosis / Thrombosis - enzymology / Thrombosis - genetics / Vascular occlusion

2017

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Host DNases prevent vascular occlusion by neutrophil extracellular traps

2017

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2017

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Journal Article

Host DNases prevent vascular occlusion by neutrophil extracellular traps

Fuchs, Tobias A.,

Long, Andy T.,

Herrmann, Martin,

Kluge, Stefan,

Renné, Thomas,

Mizuta, Ryushin,

Bilyy, Rostyslav,

Krenn, Veit,

Napirei, Markus,

Panzer, Ulf,

Panda, Rachita,

Renné, Christoph,

Jiménez-Alcázar, Miguel,

Rangaswamy, Chandini,

Simsek, Yashin J.,

Kitamura, Daisuke,

Mannherz, Hans Georg,

Bitterling, Josephine

2017

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

/ Deoxyribonuclease I - blood