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Neutrophil extracellular traps can activate alternative complement pathways
Wang, H.1,2,3,4,5; Wang, C.1,2,3,4,5; Zhao, M. -H.1,2,3,4,5; Chen, M.1,2,3,4,5
关键词Alternative Complement Pathway Anca Complement Neutrophil Extracellular Traps Vasculitis
刊名CLINICAL AND EXPERIMENTAL IMMUNOLOGY
2015-09-01
DOI10.1111/cei.12654
181期:3页:518-527
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Immunology
资助者Chinese 973 project ; National Natural Science Fund ; &prime ; National Key Technology Research and Development (R&amp ; D) Program&prime ; of the Ministry of Science and Technology of China ; Chinese 973 project ; National Natural Science Fund ; &prime ; National Key Technology Research and Development (R&amp ; D) Program&prime ; of the Ministry of Science and Technology of China
研究领域[WOS]Immunology
关键词[WOS]ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES ; ANTIBODY-ASSOCIATED VASCULITIS ; DENDRITIC CELLS ; PROTEIN C3 ; ANCA ; INHIBITION ; GENERATION ; GLOMERULONEPHRITIS ; DEPOSITION ; DISEASE
英文摘要

The interaction between neutrophils and activation of alternative complement pathway plays a pivotal role in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). ANCAs activate primed neutrophils to release neutrophil extracellular traps (NETs), which have recently gathered increasing attention in the development of AAV. The relationship between NETs and alternative complement pathway has not been elucidated. The current study aimed to investigate the relationship between NETs and alternative complement pathway. Detection of components of alternative complement pathway on NETs in vitro was assessed by immunostain and confocal microscopy. Complement deposition on NETs were detected after incubation with magnesium salt ethyleneglycol tetraacetic acid (Mg-EGTA)-treated human serum. After incubation of serum with supernatants enriched in ANCA-induced NETs, levels of complement components in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Complement factor B (Bb) and properdin deposited on NETs in vitro. The deposition of C3b and C5b-9 on NETs incubated with heat-inactivated normal human serum (Hi-NHS) or EGTA-treated Hi-NHS (Mg-EGTA-Hi-NHS) were significantly less than that on NETs incubated with NHS or EGTA-treated NHS (Mg-EGTA-NHS). NETs induced by ANCA could activate the alternative complement cascade in the serum. In the presence of EGTA, C3a, C5a and SC5b-9 concentration decreased from 80042 +/- 24481 ng/ml, 768 +/- 150 ng/ml, 38215 +/- 15975 ng/ml in the supernatants enriched in ANCA induced NETs to 47907 +/- 1562 ng/ml, 486 +/- 126 ng/ml, 21265 +/- 4440 ng/ml in the supernatants of DNase I-degraded NETs (P<0001, P = 0008, P<0001, respectively). NETs could activate the alternative complement pathway, and might thus participate in the pathogenesis of AAV.

语种英语
所属项目编号2012CB517702 ; 81425008 ; 81370829 ; 81321064 ; 2011BAI10B04
资助者Chinese 973 project ; National Natural Science Fund ; &prime ; National Key Technology Research and Development (R&amp ; D) Program&prime ; of the Ministry of Science and Technology of China ; Chinese 973 project ; National Natural Science Fund ; &prime ; National Key Technology Research and Development (R&amp ; D) Program&prime ; of the Ministry of Science and Technology of China
WOS记录号WOS:000359731700014
引用统计
被引频次:33[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52540
专题北京大学第一临床医学院_肾脏内科
作者单位1.Peking Univ, Inst Nephrol, Beijing 100034, Peoples R China
2.Minist Hlth China, Key Lab Renal Dis, Beijing, Peoples R China
3.Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China
4.Peking Univ, Hosp 1, Dept Med, Div Renal, Beijing 100034, Peoples R China
5.Peking Univ, Minist Educ, Key Lab Chron Kidney Dis Prevent & Treatment, Beijing 100034, Peoples R China
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GB/T 7714
Wang, H.,Wang, C.,Zhao, M. -H.,et al. Neutrophil extracellular traps can activate alternative complement pathways[J]. CLINICAL AND EXPERIMENTAL IMMUNOLOGY,2015,181(3):518-527.
APA Wang, H.,Wang, C.,Zhao, M. -H.,&Chen, M..(2015).Neutrophil extracellular traps can activate alternative complement pathways.CLINICAL AND EXPERIMENTAL IMMUNOLOGY,181(3),518-527.
MLA Wang, H.,et al."Neutrophil extracellular traps can activate alternative complement pathways".CLINICAL AND EXPERIMENTAL IMMUNOLOGY 181.3(2015):518-527.
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