Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
Vaccine. 2010 Jul 12;28(31):4945-54. doi: 10.1016/j.vaccine.2010.05.037.
We had isolated a high molecular weight polysaccharide fraction, designated as F3, and performed a comprehensive analysis of its immunomodulatory and adjuvant activities in vivo and in vitro. In vivo, F3-treated mice showed an increase in the number of dendritic cells as well as CD4, CD8, regulatory T, B, plasma, NK, and NKT cells in the spleen. F3 also elevated the levels of multiple cytokines and chemokines in the blood of mice. F3 displayed potent adjuvant activity for tetanus toxoid in the absence of alum and potentiated antibody responses to alum-containing tetanus toxoid in mice. In addition, F3 also boosted Th1 and Th2 response in vivo. In vitro, F3 induced the maturation of dendritic cells derived from human monocytes by upregulating CD40, CD54, CD80, CD83, CD86, and HLA-DR, enhanced mixed lymphocyte reaction, and stimulated the production of ten cytokines and six chemokines. In microarray analysis, expressions of 7688 genes were modulated in dendritic cells after treatment with F3, including cytokine and chemokine genes. These results provide F3 polysaccharide extract further insight into the mechanisms of action for these immunomodulatory and adjuvant activities of from Ganoderma lucidum and also offer preclinical evidence for its development as a vaccine adjuvant.
我们分离出了一种高分子量多糖部分,命名为 F3,并对其在体内和体外的免疫调节和佐剂活性进行了全面分析。在体内,F3 处理的小鼠脾脏中的树突状细胞以及 CD4、CD8、调节性 T、B、浆细胞、NK 和 NKT 细胞数量增加。F3 还提高了小鼠血液中多种细胞因子和趋化因子的水平。F3 在没有明矾的情况下对破伤风类毒素具有强大的佐剂活性,并增强了含明矾破伤风类毒素在小鼠中的抗体反应。此外,F3 还能在体内增强 Th1 和 Th2 反应。在体外,F3 通过上调 CD40、CD54、CD80、CD83、CD86 和 HLA-DR 诱导人单核细胞来源的树突状细胞成熟,增强混合淋巴细胞反应,并刺激十种细胞因子和六种趋化因子的产生。在微阵列分析中,用 F3 处理树突状细胞后,有 7688 个基因的表达被调节,包括细胞因子和趋化因子基因。这些结果为灵芝的这些免疫调节和佐剂活性的作用机制提供了进一步的了解,并为其作为疫苗佐剂的开发提供了临床前证据。