Impairment of Mature Dendritic Cells Derived from X-Irradiated Human Monocytes Depends on the Type of Maturation Stimulus Used
Impairment of Mature Dendritic Cells Derived from X-Irradiated Human Monocytes Depends on the Type of Maturation Stimulus Used
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DOI：
10.1667/rr2997.1
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发表时间：
2012-10-01
影响因子：
3.4
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
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作者：
Yoshino, Hironori;Kashiwakura, Ikuo
树突状细胞在免疫系统中发挥着重要作用。我们之前报道过，X射线照射的单核细胞（树突状细胞的前体）可以分化为树突状细胞，然后在肿瘤坏死因子-a刺激后在表面抗原表达方面成熟，但表现出功能降低。树突状细胞可以响应各种类型的成熟刺激而成熟。因此，本研究调查了暴露于电离辐射的单核细胞的树突状细胞是否能够对病原体衍生的成分和促炎细胞因子产生充分的反应。从哈菲层中分离出的人单核细胞暴露于X射线下，然后分化为未成熟的树突状细胞。未成熟的树突状细胞受到脂多糖（LPS）或促炎细胞因子混合物的刺激。通过表面抗原表达的发现证实，来自未照射和X照射的单核细胞的树突状细胞在LPS和促炎细胞因子混合物刺激后表现出成熟。然而，在LPS刺激后，来自X射线照射的单核细胞的树突状细胞上CD80和CD83的表达水平低于来自未照射的单核细胞的树突状细胞。在促炎细胞因子混合物刺激后没有观察到这种减少。类似地，在来自 X 射线照射的单核细胞的 LPS 刺激的树突状细胞中观察到基质金属蛋白酶 9 和细胞因子产生的损害，而在促炎细胞因子混合物刺激时没有观察到这些损害。尽管成熟刺激的类型不同，但与未照射组相比，照射组树突状细胞刺激 T 细胞的能力较低。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的类型，并且 X 射线照射会损害树突状细胞对 LPS 的反应。 (C) 2012 年放射线研究会
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-a 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 huffy 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. (C) 2012 by Radiation Research Society