Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines

C Schauer, C Janko, LE Munoz, Y Zhao, D Kienhöfer… - Nature medicine, 2014 - nature.com
C Schauer, C Janko, LE Munoz, Y Zhao, D Kienhöfer, B Frey, M Lell, B Manger, J Rech…
Nature medicine, 2014nature.com
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 …
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.
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