The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival.
The macrophage C-type lectin receptor CLEC5A (MDL-1) expression is associated with early plaque progression and promotes macrophage survival.
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巨噬细胞 C 型凝集素受体 CLEC5A (MDL-1) 表达与早期斑块进展相关并促进巨噬细胞存活
DOI：
10.1186/s12967-017-1336-z
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发表时间：
2017-11-10
影响因子：
7.4
通讯作者：
Tao R
中科院分区：
文献类型：
--
作者：
Xiong W;Wang H;Lu L;Xi R;Wang F;Gu G;Tao R
背景：早期斑块进展的生物标志物仍然难以捉摸。髓系dap12相关凝集素-1 (MDL-1)，也称为CLEC5A，是一种c型凝集素受体，与多种急慢性炎症性疾病的进展有关。然而，其水平与动脉粥样硬化之间的关系尚不清楚。在这项研究中，我们旨在探讨巨噬细胞MDL-1表达与早期动脉粥样硬化进展的相关性。方法采用免疫荧光染色、实时荧光定量PCR和western blot检测小鼠主动脉或巨噬细胞中MDL-1的表达。通过腺病毒感染和TUNEL实验进一步研究MDL-1在巨噬细胞存活中的作用。结果MDL-1在晚期人和apoE−/−小鼠动脉粥样硬化斑块中显著表达，尤其是在病变巨噬细胞中。在动脉粥样硬化回归模型中，我们发现ldlr - / -小鼠退行性斑块的病变巨噬细胞中MDL-1的表达高度下调，与病变巨噬细胞含量和M1促炎巨噬细胞标志物的减少相一致。此外，我们发现MDL-1在炎性M1亚型极化骨髓源性巨噬细胞中显著表达。在体外实验中，在斑块进展的病理生理驱动因素（如氧化低密度脂蛋白（ox-LDL）和缺氧）处理的巨噬细胞中，MDL-1水平显著升高。在机制上，我们证明了在ox-LDL刺激下，MDL-1过表达显著促进巨噬细胞存活，降低cleaved caspase-3表达，这表明它可以维持病变巨噬细胞存活并引起其积累。本研究首次证实MDL-1主要表达于动脉粥样硬化病变的巨噬细胞中，巨噬细胞MDL-1表达升高与早期斑块进展相关，促进巨噬细胞存活。
BackgroundBiomarkers of early plaque progression are still elusive. Myeloid DAP12-associating lectin-1 (MDL-1), also called CLEC5A, is a C-type lectin receptor implicated in the progression of multiple acute and chronic inflammatory diseases. However, the relationship between its level and atherosclerosis is unknown. In this study, we aimed to investigate the correlation between macrophage MDL-1 expression and early atherosclerosis progression.MethodsImmunofluorescence staining, real-time PCR and western blot were performed to analyze MDL-1 expression in aorta or mice macrophages. The role of MDL-1 in macrophage survival was further investigated by adenovirus infection and TUNEL assay.ResultsSignificant MDL-1 expression was found in advanced human and apoE−/− mice atherosclerotic plaques, especially in lesional macrophages. In the model of atherosclerosis regression, we found MDL-1 expression was highly downregulated in lesional macrophages from ldlr−/− mouse regressive plaques, coincident with a reduction in lesional macrophage content and marker of M1 proinflammatory macrophages. Furthermore, we found MDL-1 was significantly expressed in inflammatory M1 subtype polarized bone marrow-derived macrophages. In vitro experiments, the level of MDL-1 was remarkably elevated in macrophages treated with pathophysiological drivers of plaque progression, such as oxidized low-density lipoprotein (ox-LDL) and hypoxia. Mechanistically, we demonstrated that MDL-1 overexpression notably promoted macrophage survival and decreased cleaved caspase-3 expression under ox-LDL stimulation, which suggested that it could maintain lesional macrophage survival and cause its accumulation.ConclusionsThis study firstly demonstrated that MDL-1 is mainly expressed in atherosclerotic lesional macrophages and increased macrophage MDL-1 expression is associated with early plaque progression and promotes macrophage survival.
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影响因子：
3.7
作者：
Chen DY;Yao L;Chen YM;Lin CC;Huang KC;Chen ST;Lan JL;Hsieh SL
通讯作者：
Hsieh SL
影响因子：
20.3
作者：
Gautier, Emmanuel L.;Ivanov, Stoyan;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Aoki, Naoko;Kimura, Yuka;Tateno, Masatoshi
通讯作者：
Tateno, Masatoshi
影响因子：
15.9
作者：
Potteaux, Stephane;Gautier, Emmanuel L.;Randolph, Gwendalyn J.
通讯作者：
Randolph, Gwendalyn J.