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年龄相关性黄斑变性患者活化巨噬细胞的促血管生成特性

Proangiogenic characteristics of activated macrophages from patients with age-related macular degeneration.

作者信息

Hagbi-Levi Shira, Grunin Michelle, Jaouni Tareq, Tiosano Liran, Rinsky Batya, Elbaz-Hayoun Sarah, Peled Amnon, Chowers Itay

机构信息

Department of Ophthalmology, Hadassah-Hebrew University Medical Center and the Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.

Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

出版信息

Neurobiol Aging. 2017 Mar;51:71-82. doi: 10.1016/j.neurobiolaging.2016.11.018. Epub 2016 Dec 10.

Abstract

Macrophages were previously implicated in the pathogenesis of neovascular age-related macular degeneration (nvAMD). It is unclear if a specific macrophage phenotype is associated with nvAMD, and if macrophages from nvAMD patients are more pathogenic as compared with controls. To address these issues, we evaluated macrophages derived from peripheral blood monocytes of nvAMD patients and age-matched controls. Macrophages were assessed in terms of their expression profile and of their angiogenic potential in the choroid sprouting assay and the rat model of laser-induced choroidal neovascularization. Results showed a proangiogenic and inflammatory gene and protein expression profiles in classic (M[IFNγ and LPS]) and alternative (M[IL-4 and IL-13]) polarized macrophages. Furthermore, activated macrophages, particularly of the M(IFNγ and LPS) phenotype from nvAMD patients, were proangiogenic ex vivo and in vivo. These findings implicate activated human macrophages, particularly M(IFNγ and LPS) macrophages from nvAMD patients, in nvAMD. Further research is required to determine whether activated macrophages can serve as therapeutic targets in nvAMD.

摘要

巨噬细胞先前被认为与新生血管性年龄相关性黄斑变性(nvAMD)的发病机制有关。目前尚不清楚是否存在特定的巨噬细胞表型与nvAMD相关,以及与对照组相比,nvAMD患者的巨噬细胞是否更具致病性。为了解决这些问题,我们评估了来自nvAMD患者和年龄匹配对照组外周血单核细胞的巨噬细胞。在脉络膜发芽试验和激光诱导脉络膜新生血管形成的大鼠模型中,根据巨噬细胞的表达谱及其血管生成潜力对其进行了评估。结果显示,经典极化(M[IFNγ和LPS])和替代极化(M[IL-4和IL-13])的巨噬细胞中存在促血管生成和炎症相关的基因及蛋白表达谱。此外,活化的巨噬细胞,特别是来自nvAMD患者的M(IFNγ和LPS)表型巨噬细胞,在体内外均具有促血管生成作用。这些发现表明活化的人类巨噬细胞,特别是来自nvAMD患者的M(IFNγ和LPS)巨噬细胞,参与了nvAMD的发病过程。需要进一步研究以确定活化的巨噬细胞是否可作为nvAMD的治疗靶点。

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