INVESTIGAISTION AND MODELING OF LEUKOCYTE RESPONSES IN THE BLOOD TO γ- IRRADIATION USING ENERGY PARAMETERS OF IMMUNE NETWORK CELLS

G. Morozova, M. Muny'os, A. Ivanov, T. Kulinich, S. Romanov
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Abstract

Biophysical control of radiation exposure to humans in the areas of nuclear reactors, in space flight conditions, as well as during radiation therapy, is relevant today. In this regard, the following tasks were solved in this work: 1) study of the leukocytes reactions in the blood after a single exposure to 60Co γ-radiation on the blood in vitro; 2) mathematical modeling of the fast immune responses using energy indicators of cells. By use of the luminescent microscope, lymphocytes and neutrophils were recognized and examined in donor venous blood smears, vitally stained with a cationic probe 4-(n-dimethylaminostyril)-1-methylpyridinium (DSM). Cell energy activity (EA) in each population was characterized by the sum of transmembrane potentials (TMP) on the outer and mitochondrial membranes, which was assessed by DSM fluorescence intensity and color in cell mitochondria and nuclei. Dose-dependent γ-irradiation effects were evaluated on the basis of digital fluorescent images computer analysis. It was found in the experiments that the change in the TMP of after blood γ - irradiation in doses of 1Gy-5Gy depends on their initial EA. An S-shaped dose dependence was revealed for the irradiated lymphocytes energy activity. The greatest effect of cells energy decrease occurs after irradiation with 4 Gy dose. A model of T-dependent immune responses is proposed in the form a system of nonlinear differential equations before and after blood irradiation, where the concentrations for five cell populations are replaced by their fluorescent variables, which reflect the number of active mitochondria in each population. Such a model is also adequate for describing the rapid phase of the immune response after single-hit radiation exposure of the body.
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利用免疫网络细胞的能量参数研究和模拟血液中白细胞对 γ- 辐照的反应
在核反应堆领域、太空飞行条件下以及在放射治疗过程中,对人类所受辐照进行生物物理控制在当今具有现实意义。为此,本研究完成了以下任务:1)研究体外血液受到 60Co γ 辐射一次后血液中白细胞的反应;2)利用细胞的能量指标建立快速免疫反应的数学模型。利用荧光显微镜识别并检查了供体静脉血涂片中的淋巴细胞和中性粒细胞,涂片经阳离子探针 4-(正二甲氨基吡啶)-1-甲基吡啶鎓(DSM)染色。细胞外膜和线粒体膜上的跨膜电位(TMP)之和表征了每个细胞群的细胞能量活动(EA),DSM荧光强度和细胞线粒体及细胞核的颜色评估了细胞能量活动(EA)。根据数字荧光图像计算机分析评估了剂量依赖性γ-辐照效应。实验发现,在 1Gy-5Gy 剂量的血液γ-辐照后,TMP 的变化取决于其初始 EA。经辐照的淋巴细胞的能量活性呈 S 型剂量依赖关系。细胞能量下降的最大影响出现在 4 Gy 剂量照射之后。在该模型中,五个细胞群的浓度被其荧光变量所取代,荧光变量反映了每个细胞群中活跃线粒体的数量。这种模型也足以描述人体受到单次辐照后免疫反应的快速阶段。
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