Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans.
Effect of Selenium and Peroxynitrite on Immune Function of Immature Dendritic Cells in Humans.
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DOI：
10.12659/msm.929004
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发表时间：
2021-03-08
期刊：
影响因子：
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通讯作者：
Jia Y
中科院分区：
文献类型：
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作者：
Xia H;Zhang L;Dai J;Liu X;Zhang X;Zeng Z;Jia Y
已知硒和过氧亚硝酸盐支持免疫细胞（包括T细胞、B细胞和巨噬细胞）的生长和活性。然而，这些因子在人类未成熟树突状细胞（imDC）的免疫功能中的作用尚不清楚。使用Ficoll密度梯度离心分离来自血液样品的混合物的单核细胞，并在诱导为imDC之前用免疫磁珠纯化。然后，细胞接受不处理（对照组），或用亚硒酸钠（Na 2SeO 3，Se）、3-吗啉基丙酮亚胺（SIN 1，其分解成过氧亚硝酸盐）或Se+ SIN 1处理。细胞活力，迁移，抗吞噬能力，氧化应激，细胞外信号调节激酶（ERK）和MMP 2的蛋白表达进行了评估，分别使用CCK 8测定，细胞计数器和流式细胞术，微孔板分光光度计，和Western印迹分析。0.1 μmol/LNa 2SeO 3对imDCs的活性无影响，而1 mmol/LSIN 1则显著降低imDCs的活性（P<0.05）。Na_2SeO_3和SIN_1分别抑制和增强细胞的趋化迁移能力和抗吞噬能力（P<0.05）。亚硒酸钠和Se+ SIN 1均能显著提高SOD和GSH-Px活性（P<0.001）。Na_2SeO_3和SIN_1处理后，谷氨酰胺含量显著降低（P<0.05），Se+ SIN_1处理后，谷氨酰胺含量显著升高（P<0.05）。活性氧水平仅在SIN 1处理组升高（P<0.05）。Na 2SeO 3、SIN 1和Se+ SIN 1处理组ERK磷酸化水平升高，MMP 2蛋白表达降低（P<0.05）。硒和过氧亚硝酸盐可以通过调节活性氧或谷胱甘肽水平来激活ERK并促进抗原吞噬，以及通过降低MMP 2表达来抑制趋化性迁移，从而影响imDC中的免疫功能。
Selenium and peroxynitrite are known to support the growth and activity of immune cells, including T cells, B cells and macrophages. However, the role of these factors in the immune function of human immature dendritic cells (imDCs) is not clear. Monocytes from a mixture of blood samples were isolated using Ficoll density gradient centrifugation and purified with immunomagnetic beads before being induced into imDCs. Cells then either received no treatment (control group), or treatment with sodium selenite (Na2SeO3, Se), 3-morpholinosydnonimine (SIN1, which decomposes into peroxynitrite), or Se+SIN1. Cell viability, migration, and antiphagocytic abilities, oxidative stress, and protein expression of extracellular signal-regulated kinases (ERK) and MMP2 were assessed using a CCK8 assay, cell counter and flow cytometry, microplate spectrophotometer, and Western blot analysis, respectively. Viability of imDCs was unaffected by 0.1 μmol/L of Na2SeO3, although 1 mmol/L of SIN1 decreased it significantly (P<0.05). Chemotactic migration and antiphagocytic abilities were inhibited and enhanced, respectively, by treatment with Na2SeO3 and SIN1 (P<0.05). Activities of superoxide dismutase and glutathione peroxidase were increased by Na2SeO3 and Se+SIN1 (P<0.001). Glutathione content decreased with exposure to Na2SeO3 and SIN1 (P<0.05), but increased after treatment with Se+SIN1 (P<0.05). Levels of reactive oxygen species only increased with SIN1 treatment (P<0.05). Treatment with Na2SeO3, SIN1 and Se+SIN1 increased ERK phosphorylation and decreased MMP2 protein expression (P<0.05). Selenium and peroxynitrite can influence immune function in imDCs by regulating levels of reactive oxygen species or glutathione to activate ERK and promote antigen phagocytosis, as well as by decreasing MMP2 expression to inhibit chemotactic migration.