Fig. 4

HMGB1-dependent engagement of TLR2, TLR4 and RAGE contributed to NETs formation in the presence of ANCA-positive IgG. Blockage of TLR2, TLR4 and RAGE decreased DNA release by MPO-ANCA-positive IgG (a) or PR3-ANCA-positive IgG (b) in HMGB1-pretreated cells. Blockage of TLR2, TLR4 and RAGE decreased percentage of NETs formation by MPO-ANCA-positive IgG (c) or PR3-ANCA-positive IgG (d) in HMGB1-pretreated cells. Bars represent mean ± SD of repeated measurements on neutrophils of 8–9 independent experiments and 9 donors. ANCA antineutrophil cytoplasmic antibody, HMGB1 high-mobility group box 1, IgG immunoglobulin G, MPO myeloperoxidase, NETs neutrophil extracellular traps, PR3 proteinase 3, RAGE receptor for advanced glycation end products, TLR Toll-like receptor