Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils
Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathwa...
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00559/full |
| _version_ | 1811220875086659584 |
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| author | Su-Fang Chen Su-Fang Chen Su-Fang Chen Feng-Mei Wang Feng-Mei Wang Feng-Mei Wang Zhi-Ying Li Zhi-Ying Li Zhi-Ying Li Feng Yu Feng Yu Feng Yu Min Chen Min Chen Min Chen Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao |
| author_facet | Su-Fang Chen Su-Fang Chen Su-Fang Chen Feng-Mei Wang Feng-Mei Wang Feng-Mei Wang Zhi-Ying Li Zhi-Ying Li Zhi-Ying Li Feng Yu Feng Yu Feng Yu Min Chen Min Chen Min Chen Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao |
| author_sort | Su-Fang Chen |
| collection | DOAJ |
| description | Our previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil–endothelium interaction. We demonstrated that FH bound to neutrophils by immunostaining and flow cytometry. Interestingly, ANCA-induced activation of neutrophils, including respiratory burst and degranulation, was inhibited by FH. Although FH enhanced neutrophils adhesion and migration toward human glomerular endothelial cells (hGEnCs), it inhibited ANCA-induced activation of neutrophils in the coculture system of hGEnCs and neutrophils. Moreover, the activation and injury of hGEnCs, reflected by the level of endothelin-1 in the supernatant of cocultures, was markedly reduced by FH. However, we found that FH from patients with active AAV exhibited a deficient ability in binding neutrophils and inhibiting ANCA-induced neutrophil activation in fluid phase and on endothelial cells, as compared with that from healthy controls. Therefore, our findings indicate a novel role of FH in inhibiting ANCA-induced neutrophil activation and protecting against glomerular endothelial injury. However, FH from patients with active AAV are deficient in their ability to bind neutrophils and inhibit neutrophil activation by ANCA. It further extends the current understanding of the pathogenesis of AAV, thus providing potential clues for intervention strategies. |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T07:50:15Z |
| publishDate | 2018-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-be99ff2044734771bfb8a99fac0407712022-12-22T03:41:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-03-01910.3389/fimmu.2018.00559353224Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With NeutrophilsSu-Fang Chen0Su-Fang Chen1Su-Fang Chen2Feng-Mei Wang3Feng-Mei Wang4Feng-Mei Wang5Zhi-Ying Li6Zhi-Ying Li7Zhi-Ying Li8Feng Yu9Feng Yu10Feng Yu11Min Chen12Min Chen13Min Chen14Ming-Hui Zhao15Ming-Hui Zhao16Ming-Hui Zhao17Ming-Hui Zhao18Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, ChinaKey Laboratory of Renal Disease, Ministry of Health of China, Beijing, ChinaKey Laboratory of Chronic Kidney Disease Prevention and Treatment, Peking University, Ministry of Education, Beijing, ChinaPeking-Tsinghua Center for Life Sciences, Beijing, ChinaOur previous study demonstrated that plasma levels of complement factor H (FH) were inversely associated with the disease activity of patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). In addition to serving as an inhibitor of the alternative complement pathway, there is increasing evidence demonstrating direct regulatory roles of FH on several cell types. Here, we investigated the role of FH in the process of ANCA-mediated activation of neutrophils and neutrophil–endothelium interaction. We demonstrated that FH bound to neutrophils by immunostaining and flow cytometry. Interestingly, ANCA-induced activation of neutrophils, including respiratory burst and degranulation, was inhibited by FH. Although FH enhanced neutrophils adhesion and migration toward human glomerular endothelial cells (hGEnCs), it inhibited ANCA-induced activation of neutrophils in the coculture system of hGEnCs and neutrophils. Moreover, the activation and injury of hGEnCs, reflected by the level of endothelin-1 in the supernatant of cocultures, was markedly reduced by FH. However, we found that FH from patients with active AAV exhibited a deficient ability in binding neutrophils and inhibiting ANCA-induced neutrophil activation in fluid phase and on endothelial cells, as compared with that from healthy controls. Therefore, our findings indicate a novel role of FH in inhibiting ANCA-induced neutrophil activation and protecting against glomerular endothelial injury. However, FH from patients with active AAV are deficient in their ability to bind neutrophils and inhibit neutrophil activation by ANCA. It further extends the current understanding of the pathogenesis of AAV, thus providing potential clues for intervention strategies.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00559/fullfactor Hneutrophilsactivationanti-neutrophil cytoplasmic autoantibodyvasculitis |
| spellingShingle | Su-Fang Chen Su-Fang Chen Su-Fang Chen Feng-Mei Wang Feng-Mei Wang Feng-Mei Wang Zhi-Ying Li Zhi-Ying Li Zhi-Ying Li Feng Yu Feng Yu Feng Yu Min Chen Min Chen Min Chen Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao Ming-Hui Zhao Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils Frontiers in Immunology factor H neutrophils activation anti-neutrophil cytoplasmic autoantibody vasculitis |
| title | Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils |
| title_full | Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils |
| title_fullStr | Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils |
| title_full_unstemmed | Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils |
| title_short | Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils |
| title_sort | complement factor h inhibits anti neutrophil cytoplasmic autoantibody induced neutrophil activation by interacting with neutrophils |
| topic | factor H neutrophils activation anti-neutrophil cytoplasmic autoantibody vasculitis |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00559/full |
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