Cranial irradiation alters the brain's microenvironment and permits CCR2+ macrophage infiltration.
Cranial irradiation alters the brain's microenvironment and permits CCR2+ macrophage infiltration.
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DOI：
10.1371/journal.pone.0093650
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Rosi S
中科院分区：
文献类型：
--
作者：
Morganti JM;Jopson TD;Liu S;Gupta N;Rosi S
放射治疗通常用于治疗原发性或转移性中枢神经系统肿瘤。据信，神经炎症信号通路的激活有助于常见不良反应的发展，这可能最终导致认知功能障碍。最近的研究发现趋化因子（C-C基序）受体（CCR 2），组成性表达的单核细胞-巨噬细胞系的细胞，作为辐射诱导的认知障碍的介质。在本研究中，我们使用了一个独特的报告小鼠（CCR 2 RFP/+ CX 3CR 1GFP/+），以准确地描绘居民（CX 3CR 1+）与外周（CCR 2+）的先天性免疫反应在脑照射后。我们的研究结果表明，一个单一的剂量10 Gy的头部γ射线照射诱导的居民小胶质细胞的百分比显着下降，而诱导的外周来源的CCR 2+巨噬细胞的浸润增加。尽管百分比降低，但与假手术组相比，辐照动物中F4/80+活化巨噬细胞显著增加。此外，我们还发现，与假手术组相比，野生型辐射小鼠的前房中促炎细胞因子、趋化因子、粘附分子和生长因子的水平发生了变化。所有这些分子都涉及外周单核细胞向损伤组织的募集、粘附和迁移。重要的是，与血脑屏障完整性相关的多种标志物的表达没有可测量的变化;暗示外周CCR 2+巨噬细胞的浸润可能是由于炎症诱导的趋化性信号传导。累积起来，这些数据提供的证据表明，治疗水平的颅辐射足以改变大脑的稳态平衡，并允许外周来源的CCR 2+巨噬细胞的流入以及海马结构对电离辐射的区域敏感性。
Therapeutic irradiation is commonly used to treat primary or metastatic central nervous system tumors. It is believed that activation of neuroinflammatory signaling pathways contributes to the development of common adverse effects, which may ultimately contribute to cognitive dysfunction. Recent studies identified the chemokine (C-C motif) receptor (CCR2), constitutively expressed by cells of the monocyte-macrophage lineage, as a mediator of cognitive impairments induced by irradiation. In the present study we utilized a unique reporter mouse (CCR2RFP/+CX3CR1GFP/+) to accurately delineate the resident (CX3CR1+) versus peripheral (CCR2+) innate immune response in the brain following cranial irradiation. Our results demonstrate that a single dose of 10Gy cranial γ-irradiation induced a significant decrease in the percentage of resident microglia, while inducing an increase in the infiltration of peripherally derived CCR2+ macrophages. Although reduced in percentage, there was a significant increase in F4/80+ activated macrophages in irradiated animals compared to sham. Moreover, we found that there were altered levels of pro-inflammatory cytokines, chemokines, adhesion molecules, and growth factors in the hippocampi of wild type irradiated mice as compared to sham. All of these molecules are implicated in the recruitment, adhesion, and migration of peripheral monocytes to injured tissue. Importantly, there were no measureable changes in the expression of multiple markers associated with blood-brain barrier integrity; implicating the infiltration of peripheral CCR2+ macrophages may be due to inflammatory induced chemotactic signaling. Cumulatively, these data provide evidence that therapeutic levels of cranial radiation are sufficient to alter the brain’s homeostatic balance and permit the influx of peripherally-derived CCR2+ macrophages as well as the regional susceptibility of the hippocampal formation to ionizing radiation.
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影响因子：
3.4
作者：
Lee WH;Cho HJ;Sonntag WE;Lee YW
通讯作者：
Lee YW
LY6C+“炎症单核细胞”是在西尼罗河病毒脑炎中以致病方式募集的小胶质前体。
DOI：
10.1084/jem.20080421
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Getts DR;Terry RL;Getts MT;Müller M;Rana S;Shrestha B;Radford J;Van Rooijen N;Campbell IL;King NJ
通讯作者：
King NJ
影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
DOI：
10.1016/j.ijrobp.2003.09.039
发表时间：
2004-02-01
影响因子：
7
作者：
Linard, C;Marquette, C;Mathé, D
通讯作者：
Mathé, D
影响因子：
8.3
作者：
Andres RH;Choi R;Pendharkar AV;Gaeta X;Wang N;Nathan JK;Chua JY;Lee SW;Palmer TD;Steinberg GK;Guzman R
通讯作者：
Guzman R