Department of Radiological Life Sciences, Division of Medical Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
Radiat Res. 2012 Oct;178(4):280-8. doi: 10.1667/rr2997.1. Epub 2012 Aug 10.
Dendritic cells play an essential role in the immune system. We have previously reported that X-irradiated monocytes, precursors of dendritic cells, can differentiate into dendritic cells and then mature in terms of surface antigen expression after tumor necrosis factor-α stimulation, but show reduced functionality. Dendritic cells can mature in response to various types of maturation stimuli. Therefore, this study investigated whether dendritic cells from monocytes exposed to ionizing radiation can adequately respond to pathogen-derived components and proinflammatory cytokines. Human monocytes separated from buffy coats were exposed to X rays, and were then differentiated into immature dendritic cells. Immature dendritic cells were stimulated by lipopolysaccharide (LPS) or proinflammatory cytokine mixture. The dendritic cells from nonirradiated and X-irradiated monocytes showed maturation after LPS and proinflammatory cytokine mixture stimulation as confirmed by findings of surface antigen expression. Upon LPS stimulation, however, the expression levels of CD80 and CD83 on dendritic cells from X-irradiated monocytes were lower than those of dendritic cells from nonirradiated monocytes. Such reductions were not observed upon proinflammatory cytokine mixture stimulation. Similarly, an impairment of matrix metalloproteinase-9 and cytokine production was observed in LPS-stimulated dendritic cells from X-irradiated monocytes, whereas these impairments were not observed upon proinflammatory cytokine mixture stimulation. The ability of dendritic cells to stimulate T cells was lower in the irradiated group compared with the nonirradiated group despite the type of maturation stimulus. Thus, the present study suggests that the influence of X irradiation on the maturation of dendritic cells depends on the type of maturation stimulus used and that X irradiation impairs the response of dendritic cells to LPS.
树突状细胞在免疫系统中发挥着重要作用。我们之前曾报道过，经 X 射线照射的单核细胞（树突状细胞的前体细胞）在肿瘤坏死因子-α刺激下可分化为树突状细胞并进一步成熟，但其功能会降低。树突状细胞可对各种类型的成熟刺激物作出反应而成熟。因此，本研究旨在探讨经电离辐射照射的单核细胞来源的树突状细胞是否能充分响应病原体相关成分和促炎细胞因子。我们从富血小板血浆中分离出单核细胞，并用 X 射线照射，随后将其分化为未成熟的树突状细胞。用脂多糖（LPS）或促炎细胞因子混合物刺激未成熟的树突状细胞。结果显示，经 LPS 和促炎细胞因子混合物刺激后，来自未照射和照射单核细胞的树突状细胞表现出成熟，其表面抗原表达情况也得到了证实。然而，与来自未照射单核细胞的树突状细胞相比，经 LPS 刺激后，照射单核细胞来源的树突状细胞表面 CD80 和 CD83 的表达水平较低。而在促炎细胞因子混合物刺激下，未观察到这种降低。同样，在 LPS 刺激的照射单核细胞来源的树突状细胞中，基质金属蛋白酶-9 和细胞因子的产生受到抑制，而在促炎细胞因子混合物刺激下则没有这种抑制。与未照射组相比，照射组树突状细胞刺激 T 细胞的能力较低，而与成熟刺激物的类型无关。因此，本研究表明，X 射线照射对树突状细胞成熟的影响取决于所使用的成熟刺激物的类型，并且 X 射线照射会损害树突状细胞对 LPS 的反应。
