Host DNases prevent vascular occlusion by neutrophil extracellular traps

Jimenez-Alcazar M, Rangaswamy C, Panda R, Bitterling J, Simsek YJ, Long AT, Bilyy R, Krenn V, Renne C, Renne T, Kluge S, Panzer U, Mizuta R, Mannherz HG, Kitamura D, Herrmann M, Napirei M, Fuchs TA (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Science American Association for the Advancement of Science

Book Volume: 358

Pages Range: 1202-1206

Journal Issue: 6367

DOI: 10.1126/science.aam8897

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.

Authors with CRIS profile

Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Universitätsklinikum Hamburg-Eppendorf (UKE) DE Germany (DE) Ruhr-Universität Bochum (RUB) DE Germany (DE) Tokyo University of Science / 東京理科大学 (Tōkyō Rika Daigaku) JP Japan (JP) Fachärzte für Pathologie Gemeinschaftspraxis Wiesbaden DE Germany (DE) MVZ für Histologie, Zytologie und Molekulare Diagnostik DE Germany (DE) Danylo Halytsky Lviv National Medical University / Львiвський Національний Медичний Унiверситет iм. Данила Галицького UA Ukraine (UA)

How to cite

APA:

Jimenez-Alcazar, M., Rangaswamy, C., Panda, R., Bitterling, J., Simsek, Y.J., Long, A.T.,... Fuchs, T.A. (2017). Host DNases prevent vascular occlusion by neutrophil extracellular traps. Science, 358(6367), 1202-1206. https://doi.org/10.1126/science.aam8897

MLA:

Jimenez-Alcazar, Miguel, et al. "Host DNases prevent vascular occlusion by neutrophil extracellular traps." Science 358.6367 (2017): 1202-1206.

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