Macrophage plasticity in experimental atherosclerosis.
Macrophage plasticity in experimental atherosclerosis.
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DOI：
10.1371/journal.pone.0008852
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发表时间：
2010-01-25
期刊：
影响因子：
3.7
通讯作者：
Caligiuri G
中科院分区：
文献类型：
--
作者：
Khallou-Laschet J;Varthaman A;Fornasa G;Compain C;Gaston AT;Clement M;Dussiot M;Levillain O;Graff-Dubois S;Nicoletti A;Caligiuri G
在人类疾病中，巨噬细胞（MCAH）是实验性动脉粥样硬化发展和进展的核心参与者。在这项研究中，我们评估了载脂蛋白E（ApoE）基因敲除（KO）小鼠模型中与动脉粥样硬化进展相关的MMP 4表型。我们发现，骨髓来源的MIPs提交M1和M2极化特异性表达精氨酸酶（Arg）II和精氨酸I，分别。这种不同的M1和M2 M2酶表达用于评价ApoE KO小鼠动脉粥样硬化斑块横截面中M1和M2 M2酶的频率和分布。早期病变为Arg I+（M2）M3浸润。在体外，这种类型的MIBI有利于平滑肌细胞的增殖。Arg II+（M1）MlR在老年ApoE KO小鼠的病变中出现并流行，病变进展与M1对M2 MlR表型的优势相关。为了解决M2->M1转换是否可能是由于浸润细胞的表型转换，我们进行了体外复极化实验。我们发现，完全极化的膜蛋白保留了它们的可塑性，因为它们可以恢复它们的表型。Arg I-和Arg II-表达的MMPs的分布的分析也反对最近在病变中招募M1 MMPs。因此，组合的数据表明，在体内观察到的M2->M1转换是由于病变中已经存在的细胞的转换。我们的研究表明，介入工具能够恢复M2表型的M2浸润可能发挥动脉粥样硬化保护作用。
As in human disease, macrophages (MØ) are central players in the development and progression of experimental atherosclerosis. In this study we have evaluated the phenotype of MØ associated with progression of atherosclerosis in the apolipoprotein E (ApoE) knockout (KO) mouse model. We found that bone marrow-derived MØ submitted to M1 and M2 polarization specifically expressed arginase (Arg) II and Arg I, respectively. This distinct arginase expression was used to evaluate the frequency and distribution of M1 and M2 MØ in cross-sections of atherosclerotic plaques of ApoE KO mice. Early lesions were infiltrated by Arg I+ (M2) MØ. This type of MØ favored the proliferation of smooth muscle cells, in vitro. Arg II+ (M1) MØ appeared and prevailed in lesions of aged ApoE KO mice and lesion progression was correlated with the dominance of M1 over the M2 MØ phenotype. In order to address whether the M2->M1 switch could be due to a phenotypic switch of the infiltrated cells, we performed in vitro repolarization experiments. We found that fully polarized MØ retained their plasticity since they could revert their phenotype. The analysis of the distribution of Arg I- and Arg II-expressing MØ also argued against a recent recruitment of M1 MØ in the lesion. The combined data therefore suggest that the M2->M1 switch observed in vivo is due to a conversion of cells already present in the lesion. Our study suggests that interventional tools able to revert the MØ infiltrate towards the M2 phenotype may exert an atheroprotective action.