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Nat Med. 2014 May;20(5):511-7. doi: 10.1038/nm.3547. Epub 2014 Apr 28.

Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines.

Author information

1
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
2
1] Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. [2] Department of Otorhinolaryngology, Head and Neck Surgery, Section for Experimental Oncology and Nanomedicine (SEON), University Hospital Erlangen, Erlangen, Germany.
3
1] Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. [2] Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu, China.
4
Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany.
5
Department of Radiology, Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen, Germany.
6
Division of Molecular and Experimental Surgery, Department of Surgery, University of Erlangen Medical Center, Erlangen, Germany.
7
Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
8
Department of Pathology, MVZ of Pathology, Trier, Germany.
9
1] Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. [2] Institute of Rheumatology, School of Medicine, University of Belgrade, Belgrade, Serbia.
10
Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv, Ukraine.

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.

PMID:
24784231
DOI:
10.1038/nm.3547
[Indexed for MEDLINE]

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