期刊
NATURE MEDICINE
卷 20, 期 5, 页码 511-517出版社
NATURE RESEARCH
DOI: 10.1038/nm.3547
关键词
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资金
- Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg [A41, J41]
- Masterswitch project of the European Union
- SPP1468-IMMUNOBONE
- Deutsche Forschungsgemeinschaft (DFG) [GK SFB 643]
- Emerging Fields Initiative (EFI) of the Friedrich-Alexander-Universitat (FAU) Erlangen-Nuremberg
- K. und R. Wucherpfennigstiftung
- Deutsche Krebshilfe [AZ 109510]
- European Commissions (DoReMi, European Network of Excellence) [249689]
- German Research Foundation [GA 1507/1-1]
- Swedish Science Strategic foundation
- EU FP7 project Neurinox
- Austrian Science Fund FWF [J3102-B13]
- [SFB 643]
- Austrian Science Fund (FWF) [J3102] Funding Source: Austrian Science Fund (FWF)
- Austrian Science Fund (FWF) [J 3102] Funding Source: researchfish
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.
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