Wang Chen, Wang Huan, Hao Jian, Chang Dong-Yuan, Zhao Ming-Hui, Chen Min
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.
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.
Clin Immunol. 2015 Jul;159(1):47-57. doi: 10.1016/j.clim.2015.04.008. Epub 2015 Apr 28.
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.
C5a在抗中性粒细胞胞浆抗体（ANCA）介导的中性粒细胞募集和激活过程中发挥核心作用。先前的一项研究表明，C5a在调控人中性粒细胞释放高迁移率族蛋白B1（HMGB1）方面起着关键作用。当前的研究进一步探究了在ANCA诱导的中性粒细胞激活过程中C5a与HMGB1之间的相互作用。测试了HMGB1抑制剂对ANCA抗原转位、ANCA诱导的呼吸爆发以及C5a预激活的中性粒细胞脱颗粒的影响。我们发现，阻断HMGB1可降低C5a介导的ANCA抗原转位，以及ANCA诱导的C5a预激活中性粒细胞的呼吸爆发和脱颗粒。进一步的研究表明，含有HMGB1的C5a预激活中性粒细胞的上清液也会导致原代中性粒细胞的ANCA抗原转位，而阻断HMGB1则会减少这种转位。总之，阻断HMGB1可能会减弱ANCA诱导的C5a预激活中性粒细胞的激活。HMGB1与C5a之间的相互作用可能在ANCA诱导的中性粒细胞激活中发挥重要作用。
