摘要
浸润的巨噬细胞参与致病血管如新生血管性老年性黄斑变性(nAMD)。巨噬细胞来源于循环中的单核细胞和单核细胞的三个亚型存在于人类中:经典(CD14 + CD16 -),非经典(CD14-CD16 +)和中间(CD14+CD16+单核细胞)。本研究的目的是探讨循环单核细胞湿性年龄相关性黄斑变性(NAMD)的作用。流式细胞仪分析表明,来自于CX3CR1与HLA-DR表达水平较高的nAMD患者的中间的单核细胞与那些受到控制的变量相比。单核细胞从NAMD患者表示更高水平的磷酸化信号转导与转录激活因子3(PSTAT3),并产生VEGF含量较高。在脉络膜新生血管(CNV)的小鼠模型,PSTAT3表达在视网膜和RPE /脉络膜浸润的巨噬细胞表达增加,和49.24%PSTAT3的抑制细胞因子信号3(SOCS3)在LysM-Cre+/-:SOCS3fl/fl 基因缺失:导致小鼠自发性STAT3的活化,加速新生血管形成,抑制STAT3的活化利用小肽lll12抑制激光诱导的CNV。我们的研究结果表明,单核细胞特别是单核细胞的中间亚群在nAMD患者中间被激活。循环中的单核细胞STAT3的激活可能有助于在AMD脉络膜新生血管的发展。
关键词: 巨噬细胞,单核细胞,血管生成,视网膜,年龄相关性黄斑变性,细胞因子。
Current Molecular Medicine
Title:STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration
Volume: 16 Issue: 4
Author(s): M. Chen, J. Lechner, J. Zhao, L. Toth, R. Hogg, G. Silvestri, A. Kissenpfennig, U. Chakravarthy, H. Xu
Affiliation:
关键词: 巨噬细胞,单核细胞,血管生成,视网膜,年龄相关性黄斑变性,细胞因子。
摘要: Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular agerelated macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laserinduced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD.
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M. Chen, J. Lechner, J. Zhao, L. Toth, R. Hogg, G. Silvestri, A. Kissenpfennig, U. Chakravarthy, H. Xu , STAT3 Activation in Circulating Monocytes Contributes to Neovascular Age-Related Macular Degeneration, Current Molecular Medicine 2016; 16 (4) . https://dx.doi.org/10.2174/1566524016666160324130031
DOI https://dx.doi.org/10.2174/1566524016666160324130031 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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