| Title | High-mobility group box 1 potentiates antineutrophil cytoplasmic antibody-inducing neutrophil extracellular traps formation |
| Authors | Ma, Yun-Hua Ma, Tian-tian Wang, Chen Wang, Huan Chang, Dong-Yuan Chen, Min Zhao, Ming-Hui |
| Affiliation | Peking Univ, Hosp 1, Div Renal, Dept Med,Inst Nephrol, Beijing 100034, Peoples R China. Minist Hlth China, Key Lab Renal Dis, Beijing 100034, Peoples R China. Peking Univ, Key Lab Chron Kidney Dis Prevent & Treatment, Minist Educ, Beijing 100034, Peoples R China. Peking Tsinghua Ctr Life Sci, Beijing 100034, Peoples R China. Guangxi Med Univ, Div Renal, Dept Med, Affiliated Hosp 1, Nanning 530021, Guangxi Zhuang, Peoples R China. |
| Keywords | High-mobility group box 1 ANCA Neutrophil extracellular traps AUTOANTIBODY-ASSOCIATED VASCULITIS SYSTEMIC-LUPUS-ERYTHEMATOSUS ANCA-ASSOCIATED VASCULITIS (ANCA)-ASSOCIATED VASCULITIS MICROSCOPIC POLYANGIITIS RHEUMATOID-ARTHRITIS RECEPTOR 4 HMGB1 ACTIVATION NETS |
| Issue Date | 2016 |
| Publisher | ARTHRITIS RESEARCH & THERAPY |
| Citation | ARTHRITIS RESEARCH & THERAPY.2016,18. |
| Abstract | Background: Recent studies found that the circulating high-mobility group box 1 (HMGB1) levels could reflect the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). HMGB1 could prime neutrophils by increasing ANCA antigens translocation for ANCA-mediated respiratory burst and degranulation. The current study aimed to investigate whether HMGB1 participates in ANCA-induced neutrophil extracellular traps (NETs) formation, which is one of the most important pathogenic aspects in the development of AAV. Methods: NETs were induced by treating neutrophils with HMGB1 and ANCA-positive IgG in vitro. NETs formation was assessed using immunofluorescence microscopy and fluorescence probe. Antagonist for relevant receptors Toll-like receptor (TLR) 2, TLR4 and the receptor for advanced glycation end products (RAGE), as well as NADPH oxidase molecules were employed. Results: The percentage of NETs formation was significantly higher in neutrophils stimulated with HMGB1 plus ANCA-positive IgG than that in neutrophils incubated with HMGB1 or ANCA-positive IgG alone. Consistently, compared with the nonstimulated neutrophils, the cell-free DNA (cfDNA) concentration of NETs was significantly increased from 334.09 +/- 46.89 ng/ml to 563.32 +/- 122.07 ng/ml in the neutrophils incubated with HMGB1 plus MPO-ANCA-positive IgG (P < 0.001), and from 303.44 +/- 37.14 ng/ml to 563.79 +/- 145.94 ng/ml in the neutrophils incubated with HMGB1 plus PR3-ANCA-positive IgG (P < 0.001). The aforementioned effect was significantly attenuated by antagonist for relevant receptors TLR2, TLR4 and RAGE, as well as blocking NADPH oxidase. Conclusions: HMGB1 can potentiate ANCA-inducing NETs formation and may be involved in the pathogenesis of AAV. HMGB1 exerts effects on NETs formation through interaction with TLR2, TLR4 and RAGE, and the process is NADPH oxidase dependent. |
| URI | http://hdl.handle.net/20.500.11897/435473 |
| ISSN | 1478-6354 |
| DOI | 10.1186/s13075-015-0903-z |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第一医院 |
