CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice
CX3CR1 deficiency induces an early protective inflammatory environment in ischemic mice
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DOI：
10.1002/glia.22474
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发表时间：
2013-06-01
期刊：
影响因子：
6.2
通讯作者：
De Simoni, Maria-Grazia
中科院分区：
文献类型：
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作者：
Fumagalli, Stefano;Perego, Carlo;De Simoni, Maria-Grazia
关于fractalkine及其独特受体CX 3CR 1在神经系统疾病中的研究产生了相反的结果。我们已经探索了缺血（30 MCAo）小鼠中CX 3CR 1缺失对以下方面的影响：（1）脑梗死面积;（2）小胶质细胞动力学和形态学;（3）小胶质细胞/巨噬细胞（M/M）活化和极化标志物的表达。我们观察到cx 3cr 1/（26.42 +/- 7.41 mm 3，平均值+/- sd）与野生型（36.29 +/- 11.57）和cx 3cr 1/+（34.49 +/- 8.91）小鼠相比梗死较小。我们纵向分析了小胶质细胞在体内双光子显微镜前，1和短暂缺血后24小时。在整个研究过程中，cx 3cr 1/和cx 3cr 1/+小鼠中的小胶质细胞都是静止的。在cx 3cr 1/小鼠中，与cx 3cr 1/+小鼠相比，它们在基线和缺血后24小时显示出显著更高数量的分支>10 μ m，表明CX 3cr 1缺陷损害了小胶质细胞肥大/变形样形态的发育。缺血后24 h，对不同M/M标记物进行死后定量免疫组化。在cx 3cr 1/中，CD 11b（M/M活化）和CD 68（与吞噬作用相关）的免疫反应性降低，而CD 45 high（巨噬细胞和白细胞募集）的免疫反应性增加。此外，免疫反应性Ym 1（M2极化）增强，而iNOS（M1）降低。我们的数据表明，在cx 3cr 1/小鼠保护缺血损伤后的早期时间点与保护性炎症环境，其特征在于促进M2极化标志物。
The studies on fractalkine and its unique receptor CX3CR1 in neurological disorders yielded contrasting results. We have explored the consequences of CX3CR1 deletion in ischemic (30 MCAo) mice on: (1) brain infarct size; (2) microglia dynamism and morphology; (3) expression of markers of microglia/macrophages (M/M) activation and polarization. We observed smaller infarcts in cx3cr1/ (26.42 +/- 7.41 mm3, mean +/- sd) compared to wild type (36.29 +/- 11.57) and cx3cr1/+ (34.49 +/- 8.91) mice. We longitudinally analyzed microglia by in vivo two-photon microscopy before, 1 and 24 h after transient ischemia. Microglia were stationary in both cx3cr1/ and cx3cr1/+ mice throughout the study. In cx3cr1/ mice, they displayed a significantly higher number of ramifications >10 m at baseline and at 24 h after ischemia compared to cx3cr1/+ mice, indicating that CX3CR1 deficiency impaired the development of microglia hypertrophic/amoeboid morphology. At 24 h after ischemia, we performed post mortem quantitative immunohistochemistry for different M/M markers. In cx3cr1/ immunoreactivity for CD11b (M/M activation) and for CD68 (associated with phagocytosis) were decreased, while that for CD45high (macrophage and leukocyte recruitment) was increased. In addition, immunoreactivity for Ym1 (M2 polarization) was enhanced, while that for iNOS (M1) was decreased. Our data show that in cx3cr1/ mice protection from ischemia at early time points after injury is associated with a protective inflammatory milieu, characterized by the promotion of M2 polarization markers.