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学科主题临床医学
p38MAPK, ERK and PI3K Signaling Pathways Are Involved in C5a-Primed Neutrophils for ANCA-Mediated Activation
Hao, Jian1,2; Meng, Li-Qiang1; Xu, Peng-Cheng1; Chen, Min1; Zhao, Ming-Hui1
刊名PLOS ONE
2012-05-31
DOI10.1371/journal.pone.0038317
7期:5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES ; PROTEIN-KINASE ; ANTIMYELOPEROXIDASE ANTIBODIES ; MOLECULAR-STRUCTURE ; REGULATED KINASE ; GLOMERULONEPHRITIS ; MYELOPEROXIDASE ; AUTOANTIBODIES ; INHIBITION ; VASCULITIS
英文摘要

Background: The complement system is one of the important contributing factors in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). C5a and the neutrophil C5a receptor play a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. The current study further investigated the signaling pathways of C5a-mediated priming of human neutrophils for ANCA-induced neutrophil activation.

Methodology/Principal Findings: The effects of the p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190), extracellular signal-regulated kinase (ERK) inhibitor (PD98059), c-Jun N-terminal kinase (JNK) inhibitor (6o) and phosphoinositol 3-kinase (PI3K) inhibitor (LY294002) were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on C5a-induced increase in expression of membrane-bound PR3 (mPR3) on neutrophils. For C5a-primed neutrophils for MPO-ANCA-induced respiratory burst, the mean fluorescence intensity (MFI) value was 254.8 +/- 67.1, which decreased to 203.6 +/- 60.3, 204.4 +/- 36.7, 202.4 +/- 49.9 and 188 +/- 47.9 upon pre-incubation with SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.05), respectively. For PR3-ANCA-positive IgG, the MFI value increased in C5a-primed neutrophils, which decreased upon pre-incubation with above-mentioned inhibitors. The lactoferrin concentration increased in C5a-primed neutrophils induced by MPO or PR3-ANCA-positive IgG supernatant and decreased upon preincubation with above-mentioned three inhibitors. mPR3 expression increased from 923.3 +/- 182.4 in untreated cells to 1278.3 +/- 299.3 after C5a treatment and decreased to 1069.9 +/- 188.9, 1100 +/- 238.2, 1092.3 +/- 231.8 and 1053.9 +/- 200.3 by SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.01), respectively.

Conclusions/Significance: Activation of p38MAPK, ERK and PI3K are important steps in the translocation of ANCA antigens and C5a-induced activation of neutrophils by ANCA.

语种英语
WOS记录号WOS:000305338500129
项目编号2012CB517702 ; 30972733 ; 81021004
资助机构Chinese 973 project ; National Natural Science Fund
引用统计
被引频次:40[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/400002259/62117
专题北京大学第一临床医学院_肾脏内科
作者单位1.Peking Univ, Minist Hlth China, Key Lab Renal Dis, Renal Div,Dept Med,Inst Nephrol,Hosp 1, Beijing 100871, Peoples R China
2.Inner Mongolia Med Coll, Affiliated Hosp, Dept Med, Div Renal, Hohhot, Inner Mongolia, Peoples R China
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Hao, Jian,Meng, Li-Qiang,Xu, Peng-Cheng,et al. p38MAPK, ERK and PI3K Signaling Pathways Are Involved in C5a-Primed Neutrophils for ANCA-Mediated Activation[J]. PLOS ONE,2012,7(5).
APA Hao, Jian,Meng, Li-Qiang,Xu, Peng-Cheng,Chen, Min,&Zhao, Ming-Hui.(2012).p38MAPK, ERK and PI3K Signaling Pathways Are Involved in C5a-Primed Neutrophils for ANCA-Mediated Activation.PLOS ONE,7(5).
MLA Hao, Jian,et al."p38MAPK, ERK and PI3K Signaling Pathways Are Involved in C5a-Primed Neutrophils for ANCA-Mediated Activation".PLOS ONE 7.5(2012).
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