Neutrophil Extracellular Traps and Microcrystals.

Balázs Rada

doi:10.1155/2017/2896380

Abstract

Neutrophil extracellular traps represent a fascinating mechanism by which PMNs entrap extracellular microbes. The primary purpose of this innate immune mechanism is thought to localize the infection at an early stage. Interestingly, the ability of different microcrystals to induce NET formation has been recently described. Microcrystals are insoluble crystals with a size of 1–100 micrometers that have different composition and shape. Microcrystals have it in common that they irritate phagocytes including PMNs and typically trigger an inflammatory response. This review is the first to summarize observations with regard to PMN activation and NET release induced by microcrystals. Gout-causing monosodium urate crystals, pseudogout-causing calcium pyrophosphate dehydrate crystals, cholesterol crystals associated with atherosclerosis, silicosis-causing silica crystals, and adjuvant alum crystals are discussed.

Highlights

NET formation is a breathtaking mechanism by which neutrophil granulocytes (PMNs) trap extracellular pathogens (Figure 1) [1]
Monosodium Urate Crystals (MSU) crystal-induced PMN activation is a critical step in this inflammatory cascade and understanding its mechanism is crucial to developing novel anti-inflammatory therapies for gout
In a recent study performed by Sil et al, we found that PMNs need to attempt to phagocytose MSU crystals in order to perform subsequent NET release and to form aggregated NETs (aggNETs) [23]

Summary

Neutrophil Extracellular Traps

NET formation is a breathtaking mechanism by which neutrophil granulocytes (PMNs) trap extracellular pathogens (Figure 1) [1]. At the early stage of gout flares, IL-1β drives inflammation, PMN recruitment and activation (proinflammatory segment), NETs become important later when sufficient levels accumulated capable of aggNET formation and cytokine degradation (anti-inflammatory phase) The details of this complex in vivo mechanism are, not well-understood. We and others showed that anakinra, a potent IL-1 receptor antagonist, and antibodies neutralizing IL-1β inhibit the NETosis-enhancing effect of macrophages and gout synovial fluid [25, 28] These results add a novel mechanism by which anakinra works and describe IL-1β as a potentiator of NET formation linking two significant arms of the inflammatory cascade in gout, inflammasome activation in macrophages, and NET formation in PMNs. A recent work by Pieterse et al emphasized the critical role of phagocytes engulfing small urate microaggregates (SMA) in hyperuricemic blood [44]. Phagocytes take up SMAs and prevent the formation of MSU crystals and NETs in the circulation [44]

Cholesterol Crystals

Silica Crystals

Conclusion