Neutrophil extracellular trap clearance by synovial macrophages in gout

Abstract

Background 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. Methods Synovial 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. Results Synovial 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. Conclusion Synovial 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.