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首页> 外文期刊>Radiation Research: Official Organ of the Radiation Research Society >Monocyte Polarization is Altered by Total-Body Irradiation in Male Rhesus Macaques: Implications for Delayed Effects of Acute Radiation Exposure
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Monocyte Polarization is Altered by Total-Body Irradiation in Male Rhesus Macaques: Implications for Delayed Effects of Acute Radiation Exposure

机译：单核细胞极化通过雄性恒河猕猴的全身照射来改变：对急性辐射暴露的延迟影响的影响

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Radiation-induced fibrosis (RIF) is a common delayed effect of acute ionizing radiation exposure (DEARE) affecting diverse tissues including the heart, lungs, liver and skin, leading to reduced tissue function and increased morbidity. Monocytes, which may be classified into classical (CD14(++), CD16(-)), intermediate (CD14(++), CD16(+)) and non-classical (CD14(+/low), CD16(++)) subtypes in humans and non-human primates (NHPs), and monocyte-derived macrophages may play an integral role in the pathogenesis of RIF. We tested the hypothesis that moderate to high levels of total-body exposure to radiation would alter monocyte polarization and produce phenotypes that could promote multi-organ fibrosis in a well-established NHP model of DEARE. Subjects were 16 young adult male rhesus macaques, ten of which were exposed to high-energy, 4 Gy X-ray total-body irradiation (TBI) and six that received sham irradiation (control). Total monocytes assessed by complete blood counts were 89% depleted in TBI animals by day 9 postirradiation (P < 0.05), but recovered by day 30 postirradiation and did not differ from control levels thereafter. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) and sorted into classical, intermediate and non-classical subsets using fluorescence-activated cell sorting (FACS) prior to and at 6 months postTBI. At 6 months postirradiation, monocyte polarization shifted towards lower classical (92% -> 86%) and higher intermediate (7% -> 12%) and non-classical monocyte subsets (0.6% -> 2%) (all P < 0.05) in TBI animals compared to baseline. No change in monocyte subsets was observed in control animals. Transcriptional profiles in classical and intermediate monocyte subsets were assessed using RNAseq. Classical monocyte gene expression did not change significantly over time or differ cross-sectionally between TBI and control groups. In contrast, significant numbers of differentially expressed genes (DEGs) were detected in intermediate monoc
机译：辐射诱导的纤维化（RIF）是急性电离辐射曝光（Deve）的常见延迟效果，影响包括心脏，肺，肝脏和皮肤的多种组织，导致组织功能减少和发病率增加。单核细胞，其可以分为古典（CD14（++），CD16（ - ）），中间体（CD14（++），CD16（+））和非古典（CD14（+ /低），CD16（++ ））人和非人类原始化物（NHPS）和单核细胞衍生的巨噬细胞中的亚型可能在RIF的发病机制中发挥积分作用。我们测试了中度到高水平的全身暴露于辐射的假设会改变单核细胞偏振并产生能够在熟悉的Deare的NHP模型中促进多器官纤维化的表型。受试者是16名年轻成人雄性恒河猴，其中十分之一暴露在高能，4 Gy X射线全身照射（TBI）和接受虚假照射（对照）的六个。通过完全血统评估的总单核细胞在第9天PayerAiradiation（P <0.05）中耗尽了89％的TBI动物（P <0.05），但在30天的时间后回收，此后没有与对照水平不同。从外周血单核细胞（PBMC）中分离单核细胞，并使用在PostTBI之前和6个月之前使用荧光激活的细胞分选（FACS）分类到经典的，中间和非古典亚组中。在6个月后，单核细胞极化朝向较低的经典（92％ - 86％）和更高的中间体（7％ - > 12％）和非经典单核细胞亚群（0.6％ - > 2％）（所有P <0.05）在TBI动物与基线相比。在对照动物中观察到单核细胞子集没有变化。使用RNASEQ评估经典和中间单核细胞亚组中的转录谱。经典单核细胞基因表达在TBI和对照组之间不显着变化或不同的横截面。相反，在中间单杂交中检测到显着数量的差异表达基因（DEGS）

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