Department of General Surgery, First Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Heping District, Shenyang 110001, China.
Int Immunopharmacol. 2013 Nov;17(3):843-9. doi: 10.1016/j.intimp.2013.09.011. Epub 2013 Oct 3.
Interferons are made by cells in response to appropriate stimuli such as viruses, bacteria, parasites or tumor cells and are released into the surrounding medium. They then bind to receptors on target cells to allow for communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors. IFN-α is produced by leukocytes and is mainly involved in innate immune response against viral or bacterial infections and for tumor control. The aim of this work is to explore the detailed modulation of IFN-α on phenotypic and functional maturation inside and outside murine bone marrow derived dendritic cells (BMDCs). The maturity of BMDCs post treatment with IFN-α was evaluated with conventional light microscope and transmission electron microscopy (TEM) for morphology changes; flow cytometry (FCM) for changes of surface molecules on BMDCs; cytochemistry, acid phosphatase activity (ACP) test, and FITC-dextran bio-assay for biochemistry analysis and enzyme-linked immunosorbent assay (ELISA) for cytokine production by BMDCs. We have shown that IFN-α 1) up-regulates the expression of MHC II, CD40, CD83, CD80 and CD86 molecules on BMDCs; 2) down-regulates the rates of pinocytosis and phagocytosis by BMDCs as evidenced by the results of decreased ACP, and FITC-dextran bio-assay; 3) enhances the ability of BMDCs to drive T cell function; and 4) induces higher levels of IL-12 and TNF-α secreted by BMDCs. Therefore, we conclude that IFN-α can efficiently promote the maturation of BMDCs through detailed modulation inside and outside BMDCs. Our study has provided more detailed data on changes of BMDCs modulated by IFN-α, and rationale on future application of IFN-α for enhancing host immunity and potent adjuvant administration in the design of DC-based vaccines.
干扰素是细胞对适当刺激(如病毒、细菌、寄生虫或肿瘤细胞)作出反应而产生的,并释放到周围介质中。然后,它们与靶细胞上的受体结合,允许细胞之间进行通信,从而触发免疫系统的保护防御,消灭病原体或肿瘤。IFN-α 由白细胞产生,主要参与针对病毒或细菌感染的固有免疫反应和肿瘤控制。本工作旨在探讨 IFN-α 对鼠骨髓来源树突状细胞(BMDCs)内外表型和功能成熟的详细调节作用。用常规显微镜和透射电子显微镜(TEM)观察 IFN-α 处理后 BMDCs 的形态变化,用流式细胞术(FCM)观察 BMDCs 表面分子的变化,用细胞化学、酸性磷酸酶活性(ACP)试验和 FITC-葡聚糖生物测定法进行生物化学分析,用酶联免疫吸附试验(ELISA)检测 BMDCs 的细胞因子产生情况,评估 BMDCs 的成熟度。我们已经表明,IFN-α 1)上调 BMDCs 上 MHC II、CD40、CD83、CD80 和 CD86 分子的表达;2)下调 BMDCs 的胞饮和吞噬作用率,这一点从 ACP 和 FITC-葡聚糖生物测定法的结果下降得到证实;3)增强 BMDCs 驱动 T 细胞功能的能力;4)诱导 BMDCs 分泌更高水平的 IL-12 和 TNF-α。因此,我们得出结论,IFN-α 可以通过对 BMDCs 内外的详细调节,有效地促进 BMDCs 的成熟。我们的研究为 IFN-α 调节 BMDCs 变化提供了更详细的数据,并为未来应用 IFN-α 增强宿主免疫和作为有效的佐剂在基于 DC 的疫苗设计中的应用提供了依据。