Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines

Schauer C, Janko C, Munoz Becerra L, Zhao Y, Kienhöfer D, Frey B, Lell M, Manger B, Rech J, Naschberger E, Holmdahl R, Krenn V, Harrer T, Jeremic I, Bilyy R, Schett G, Hoffmann M, Herrmann M (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Nature Medicine Nature Publishing Group

Book Volume: 20

Pages Range: 511-517

Journal Issue: 5

DOI: 10.1038/nm.3547

Abstract

Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.

Authors with CRIS profile

Christina Janko Einrichtungen, die zum Universitätsklinikum Erlangen gehören Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Deborah Kienhöfer Professur für Genetik Benjamin Frey Department of Radiation Oncology Michael Lell Medizinische Fakultät Bernhard Manger Professur für Rheumatologie und Klinische Immunologie Elisabeth Naschberger Medizinische Fakultät Thomas Harrer Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz Georg Schett Lehrstuhl für Innere Medizin III Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

MVZ Medizinisches Versorgungszentrum für Histologie, Zytologie und Molekulare Diagnostik Trier DE Germany (DE) Karolinska Institute SE Sweden (SE) National Academy of Sciences of Ukraine (NAN) / Національна академія наук України UA Ukraine (UA)

How to cite

APA:

Schauer, C., Janko, C., Munoz Becerra, L., Zhao, Y., Kienhöfer, D., Frey, B.,... Herrmann, M. (2014). Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nature Medicine, 20(5), 511-517. https://doi.org/10.1038/nm.3547

MLA:

Schauer, Christine, et al. "Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines." Nature Medicine 20.5 (2014): 511-517.

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