Involvement of high mobility group box 1 in the activation of C5a-primed neutrophils induced by ANCA.
C5a plays a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. A previous study showed that C5a played a crucial role in the regulation of high mobility group box 1 (HMGB1) release from human neutrophils. The current study further investigated the interaction between C5a and HMGB1 in ANCA-induced neutrophil activation. The effects of HMGB1 inhibitors on the translocation of ANCA antigens, ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils were tested. We found that blocking HMGB1 decreased C5a-mediated translocation of ANCA antigens, as well as ANCA-induced respiratory burst and degranulation of C5a-primed neutrophils. Further study showed that supernatant of C5a-primed neutrophils, which contained HMGB1, also caused translocation of ANCA antigens of primary neutrophils, whereas blocking HMGB1 decreased the translocation. In conclusion, blocking HMGB1 may attenuate ANCA-induced activation of C5a-primed neutrophils. The interaction between HMGB1 and C5a might play an important role in ANCA-induced neutrophil activation.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
Chen
C
Wang
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
Huan
H
Wang
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
Jian
J
Hao
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
Dong-Yuan
DY
Chang
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China.
Ming-Hui
MH
Zhao
Renal Division, Department of Medicine, Peking University First Hospital, Beijing 100034, China; Peking University Institute of Nephrology, Beijing 100034, China; Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China; Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, China; Peking-Tsinghua Center for Life Sciences, Beijing 100034, China. Electronic address: chenmin74@sina.com.
Min
M
Chen
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D015550:Cell Degranulation / Q000187:drug effects*; D015936:Complement C5a / Q000276:immunology / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053146:Myeloblastin / Q000187:drug effects / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects
D019268:Antibodies, Antineutrophil Cytoplasmic; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D015936:Complement C5a; D009195:Peroxidase; D053146:Myeloblastin
ANCA; C5a; HMGB1; Neutrophils