Neutrophil extracellular trap clearance by synovial macrophages in gout

Ji Hye Jeong,Bin Yoo,Seokchan Hong,Yong-Gil Kim,Chang-Keun Lee,Soo Min Ahn,Ji Seon Oh,Su Jin Choi

doi:10.1186/s13075-021-02472-4

Ji Hye Jeong, Bin Yoo + Show 6 more

Open Access

https://doi.org/10.1186/s13075-021-02472-4

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Abstract

BackgroundMonosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs). We investigated whether synovial macrophages could clear NETs as a self-resolution mechanism in acute gouty arthritis.MethodsSynovial fluid mononuclear cells (SFMCs) were incubated with NETs induced by MSU crystals. NET engulfment was determined based on neutrophil elastase (NE), myeloperoxidase (MPO), and SYTOX Green signals within synovial fluid CD14+ cells. In addition, the correlations between CD14+ cells, MPO-dsDNA complexes, and expression of pro- and anti-inflammatory cytokines were analyzed in the synovial fluid CD14+ macrophages of patients with gouty arthritis.ResultsSynovial fluid CD14+ macrophages significantly engulfed the MSU crystal-induced NETs, as evidenced by the alteration in SYTOX Green intensity or the presence of NE and MPO in the cytoplasm of CD14+ cells. The proportion of CD14+ macrophages was significantly and inversely correlated with levels of MPO-dsDNA complex in the synovial fluid of gout patients. Synovial fluid CD14+ macrophages cultured with NETs did not show a significant induction in pro- and anti-inflammatory cytokines.ConclusionSynovial fluid macrophages may play an important role in the resolution of MSU crystal-induced gouty inflammation by clearing NETs without causing any significant immunological response.

Highlights

Monosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs)
Considering that MSU crystals are well-known NRLP3 inflammasome activators, we examined the effect of the NLRP3 inflammasome pathway on NET uptake
These findings indicate that CD14+ macrophages in the synovial fluid mononuclear cells (SFMCs) of patients with gout have a capacity to engulf NETs, in the presence of MSU crystals

Summary

Introduction

Monosodium urate (MSU) crystals, i.e., the central etiological factors in gouty arthritis, induce the formation of neutrophil extracellular traps (NETs). We investigated whether synovial macrophages could clear NETs as a self-resolution mechanism in acute gouty arthritis. Our recent study showed that monocytes/macrophages from the synovial fluid of gout patients exhibit anti-inflammatory as well as pro-inflammatory properties [14]. Little is known about the interaction between immune effectors during the resolution process of gouty arthritis. In this respect, it remains largely unknown as to how immune cells recognize and respond to NETs generated in response to MSU crystals. Given that recent studies showed that macrophages are involved in clearing NETs by engulfing and degrading them [15,16,17], we here investigated whether monocytes/macrophages in the joints are involved in NET clearance in gouty arthritis

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