Tophi Defined: Neutrophil NETS, Out of Control

Schauer C, Janko C, Munoz LE, et al. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nature Medicine 20:511–517 (2014) doi:10.1038/nm.3547 Published online 28 April 2014

As they are being studied, neutrophil extracellular traps (NETs) are starting to resemble the tophi of gout, and gout is starting to resemble a defect in control of their inflammatory processes.

Neutrophils recruited to sites of inflammation undergo oxidative burst and produce reactive oxygen species. They eject chromatin, bactericidal molecules, and granular enzymes into the extracellular space to form NETs, which immobilize and kill extracellular pathogens.

At low densities, the neutrophils release pro-inflammatory mediators. But at high densities, the neutrophils release anti-inflammatory mediators that provide a negative feedback and control the process.

Neutrophils respond to pathogens, but monosodium urate (MSU) crystals can also induce neutrophilic inflammation and aggregation of NETs.

These researchers show that gouty tophi are composed of extended areas of extracellular DNA co-localizing with material from neutrophil granules. In gout patients the NET mechanism is impaired, they say, and thus the inflammation from MSU crystals is uncontrolled and persistent.