Holen Elisabeth, Bjørge Oddvin A, Jonsson Roland
Broegelmann Research Laboratory, University of Bergen, Bergen, Norway.
Nutrition. 2005 Oct;21(10):1003-9. doi: 10.1016/j.nut.2005.03.003.
The immune system is dependent on purines and pyrimidines as building blocks for DNA and RNA synthesis to enable rapid cell proliferation and protein synthesis. Emerging evidence suggests that dietary nucleotides optimize immune function. We investigated whether growth and function of human immune cells were affected by an exogenous source of nucleotides during specific antigen challenge.
Peripheral blood mononuclear cells from healthy individuals (n = 10) were stimulated with influenza virus antigen and DNA-Na+ from fish soft roe, RNA from bakers yeast (Saccharomyces cerevisiae), 2'deoxyadenosine 5'-monophosphate sodium, 2'deoxycytidine 5'-monophosphate sodium, 2'deoxyguanosine 5'-monophosphate sodium, or 2'deoxyuridine 5'-monophosphate disodium. Growth effects were ascertained by measuring the amount of tritium-labeled Thymidine 5'-monophosphate sodium incorporated into cell DNA. Cell function was measured by detection of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha, and interleukin-10 production.
Specific nucleotide derivatives alone did not affect the growth of healthy peripheral blood mononuclear cells. However, the nucleotide derivatives influenced immune cell growth and cytokine secretion when cocultured with specific antigen. DNA, RNA, deoxyadenosine monophosphate, deoxycytidine monophosphate, and deoxyuridine monophosphate increased influenza virus antigen-induced immune cell proliferation. In contrast, deoxyadenosine monophosphate and thymosine monophosphate inhibited the antigen-induced growth response. RNA and deoxyadenosine monophosphate cocultured with virus antigen significantly increased peripheral blood mononuclear cell secretion of IFN-gamma, interleukin-10, and tumor necrosis factor-alpha. DNA increased virus antigen-induced immune cell secretion of IFN-gamma only, whereas deoxyuridine monophosphate significantly increased secretion of interleukin-10 only. Deoxyguanosine monophosphate completely inhibited virus-triggered IFN-gamma secretion, whereas thymosine monophosphate did not change the secretion pattern of measured cytokines.
Nucleotide derivatives affect growth and function of specific virus antigen-stimulated human immune cells in vitro.
免疫系统依赖嘌呤和嘧啶作为DNA和RNA合成的基本组成部分，以实现快速的细胞增殖和蛋白质合成。新出现的证据表明，膳食核苷酸可优化免疫功能。我们研究了在特定抗原刺激期间，外源性核苷酸来源是否会影响人类免疫细胞的生长和功能。
用流感病毒抗原和来自鱼软卵的DNA-Na+、面包酵母（酿酒酵母）的RNA、2'-脱氧腺苷5'-单磷酸钠、2'-脱氧胞苷5'-单磷酸钠、2'-脱氧鸟苷5'-单磷酸钠或2'-脱氧尿苷5'-二磷酸钠刺激来自健康个体（n = 10）的外周血单核细胞。通过测量掺入细胞DNA中的氚标记胸腺嘧啶5'-单磷酸钠的量来确定生长效应。通过检测干扰素-γ（IFN-γ）、肿瘤坏死因子-α和白细胞介素-10的产生来测量细胞功能。
单独的特定核苷酸衍生物不影响健康外周血单核细胞的生长。然而，当与特定抗原共培养时，核苷酸衍生物会影响免疫细胞的生长和细胞因子分泌。DNA、RNA、脱氧腺苷单磷酸、脱氧胞苷单磷酸和脱氧尿苷单磷酸增加了流感病毒抗原诱导的免疫细胞增殖。相比之下，脱氧腺苷单磷酸和胸腺嘧啶单磷酸抑制了抗原诱导的生长反应。与病毒抗原共培养的RNA和脱氧腺苷单磷酸显著增加了外周血单核细胞IFN-γ、白细胞介素-10和肿瘤坏死因子-α的分泌。DNA仅增加病毒抗原诱导的免疫细胞IFN-γ的分泌，而脱氧尿苷单磷酸仅显著增加白细胞介素-10的分泌。脱氧鸟苷单磷酸完全抑制病毒触发的IFN-γ分泌，而胸腺嘧啶单磷酸没有改变所测细胞因子的分泌模式。
核苷酸衍生物在体外影响特定病毒抗原刺激的人类免疫细胞的生长和功能。
