M1 macrophages are required for murine cerebral aneurysm formation.
M1 macrophages are required for murine cerebral aneurysm formation.
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DOI：
10.1136/neurintsurg-2016-012911
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发表时间：
2018-01
影响因子：
4.8
通讯作者：
Hoh BL
中科院分区：
文献类型：
--
作者：
Nowicki KW;Hosaka K;Walch FJ;Scott EW;Hoh BL
巨噬细胞和中性粒细胞分别与脑动脉瘤的形成有关。不同髓系亚群之间的相互作用和巨噬细胞表型随时间的变化在这些病变中的作用尚不清楚。本研究的目的是检测脑动脉瘤中巨噬细胞的表型变化。我们在C57BL/6小鼠中诱导了动脉瘤的形成，并对有或没有中性粒细胞阻断的动脉瘤标本中M1和M2巨噬细胞的贡献进行了量化。在我们的动脉瘤模型中，结扎左颈总动脉和右肾动脉，并将小鼠置于高血压高脂饮食中。1周后，在基底池内立体定向注射弹性酶溶液。植入血管紧张素II分泌型渗透泵。然后用抗CXCL1抗体或免疫球蛋白对照抗体处理小鼠。分别于术后3天、1周或2周处死动物。用免疫组织化学方法分析Willis环的M1和M2巨噬细胞表型。随着时间的推移，脑动脉瘤形成中的促炎性M1/M2比率增加，从3天的0.56上升到2周的1.75(p<；0.0001)。相反，抗CXCL1抗体阻断导致向抗炎表型分化，2周时M1/M2比为0.95，与免疫球蛋白治疗组相比(p=0.0007)。CXCL1依赖的中性粒细胞炎症似乎在脑动脉瘤发展过程中巨噬细胞向M1表型极化过程中起着重要作用。
Macrophages and neutrophils have been separately implicated in cerebral aneurysm formation. The interactions between different myeloid subsets and the contributions of macrophage phenotypes in these lesions over time are not known. The purpose of the study was to examine macrophage phenotypic changes in cerebral aneurysms. We induced aneurysm formation in C57BL/6 mice and quantified contributions of M1 and M2 macrophages in aneurysm specimens with or without neutrophil blockade. In our aneurysm model, the left common carotid and right renal arteries were ligated, and mice were placed on a hypertensive high fat diet. One week later, stereotactic injection with elastase solution into the basal cisterns was performed. An angiotensin II secreting osmotic pump was implanted. The mice were then treated with anti-CXCL1 antibody or IgG control antibody. Animals were euthanized at 3 days, or 1 or 2 weeks. The circle of Willis was analyzed using immunohistochemistry for M1 and M2 macrophage phenotype contributions. Proinflammatory M1/M2 ratio increased in cerebral aneurysm formation over time, from 0.56 at 3 days to 1.75 at 2 weeks (p<0.0001). In contrast, anti-CXCL1 antibody blockade led to polarization towards an anti-inflammatory phenotype with an M1/M2 ratio of 0.95 at 2 weeks compared with IgG treated mice (p=0.0007). CXCL1 dependent neutrophil inflammation appears to have an important role in macrophage polarization to M1 phenotype in cerebral aneurysm development.
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DOI：
10.1038/mtna.2016.71
发表时间：
2016-09-27
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
20.1
作者：
Randolph GJ
通讯作者：
Randolph GJ
影响因子：
32.4
作者：
Tsuda, Y;Takahashi, H;Suzuki, F
通讯作者：
Suzuki, F
DOI：
10.1097/nen.0000000000000105
发表时间：
2014-09-01
影响因子：
3.2
作者：
Ollikainen, Eliisa;Tulamo, Riikka;Kovanen, Petri T.
通讯作者：
Kovanen, Petri T.
影响因子：
7.3
作者：
Chávez-Galán L;Olleros ML;Vesin D;Garcia I
通讯作者：
Garcia I