Aggregated Neutrophils Limit Inflammation

An analysis of the aggNETs from wild-type mice revealed that they contained only two proinflammatory mediators: IL-8 and the antiinflammatory IL-1 receptor antagonist (i.e., IL-1RA). The aggNETs appeared to degrade other inflammatory mediators via proteinase 3 and elastase. The neutrophil elastase activity was limited to aggNETs and was not present in neutrophils that were stimulated in the absence of NETosis. Thus, the authors concluded that NET aggregation results in the degradation of inflammatory mediators released by activated neutrophils. In this way, NETs can limit the inflammatory response.

The investigators were able to reduce the neutrophilic inflammation in NETosis-deficient mice by adoptive transfer of aggNETs. Taken together, the data further support the understanding that neutrophils and NETosis promote the resolution of neutrophilic inflammation. The authors conclude by suggesting that future therapies might exploit this pathway by promoting the aggregation of NETs and shifting the balance toward the resolution of inflammation. (posted 6/30/14)

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

Reference
Schauer C, Janko C, Munoz LE, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. 2014. Nat Med. May;20(5):511-517.