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巨噬细胞 A 类清道夫受体在激光诱导的小鼠脉络膜新生血管模型中的作用。

The role of macrophage class a scavenger receptors in a laser-induced murine choroidal neovascularization model.

机构信息

Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.

出版信息

Invest Ophthalmol Vis Sci. 2013 Sep 5;54(9):5959-70. doi: 10.1167/iovs.12-11380.

Abstract

PURPOSE

Laser-induced choroidal neovascularization (CNV) is a widely used model to mimic many features of CNV resulting from wet AMD. Macrophages have been implicated in the pathogenesis of AMD. Class A scavenger receptors, scavenger receptor-A (SR-A) and macrophage receptor with collagenous domain (MARCO), are expressed on macrophages and are associated with macrophage function. The goal of this study is to examine the role of macrophage scavenger receptors in immune cell recruitment and the formation of CNV.

METHODS

Laser photocoagulation was performed in wild-type and knockout mice with deletion of SR-A (SR-A(-/-)), MARCO (MARCO(-/-)), or both SR-A and MARCO double knockout (DKO). Immune cell recruitment at different time points and CNV lesions at 14 days after laser treatment were evaluated through immunostaining and confocal microscopy. Microarray analysis was performed in eyes 1 day after laser injury.

RESULTS

Wild-type eyes showed higher chemokine/receptor expression compared with knockout eyes after laser injury. Scavenger receptor deficiency markedly impaired the recruitment of neutrophils and macrophages to CNV lesions at 1- and 3-days post laser injury, respectively. Significantly reduced CNV volumes were found in the eyes from scavenger receptor knockout mice compared with wild-type mice.

CONCLUSIONS

The deficiency of scavenger receptors impairs the formation of CNV and immune cell recruitment. Our findings suggest a potential role for scavenger receptors in contributing to CNV formation and inflammation in AMD.

摘要

目的

激光诱导脉络膜新生血管(CNV)是一种广泛用于模拟湿性年龄相关性黄斑变性(AMD)导致的 CNV 的模型。巨噬细胞被认为与 AMD 的发病机制有关。A 类清道夫受体,清道夫受体-A(SR-A)和巨噬细胞胶原域受体(MARCO),在巨噬细胞上表达,并与巨噬细胞功能相关。本研究的目的是研究巨噬细胞清道夫受体在免疫细胞募集和 CNV 形成中的作用。

方法

在野生型和缺失 SR-A(SR-A(-/-))、MARCO(MARCO(-/-))或 SR-A 和 MARCO 双缺失(DKO)的敲除小鼠中进行激光光凝。通过免疫染色和共聚焦显微镜评估激光治疗后不同时间点的免疫细胞募集和 14 天后的 CNV 病变。在激光损伤后 1 天对眼睛进行微阵列分析。

结果

与敲除眼相比,野生型眼在激光损伤后显示出更高的趋化因子/受体表达。清道夫受体缺失显著损害了中性粒细胞和巨噬细胞在激光损伤后 1 天和 3 天分别向 CNV 病变的募集。与野生型小鼠相比, scavenger 受体敲除小鼠的 CNV 体积明显减少。

结论

scavenger 受体的缺失损害了 CNV 的形成和免疫细胞的募集。我们的发现表明 scavenger 受体在 AMD 中对 CNV 形成和炎症的形成具有潜在作用。

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