Pollen-Induced Oxidative Stress Influences Both Innate and Adaptive Immune Responses via Altering Dendritic Cell Functions

Pollen-Induced Oxidative Stress Influences Both Innate and Adaptive Immune Responses via Altering Dendritic Cell Functions
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DOI:
10.4049/jimmunol.0803938
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发表时间:
2010-03-01
影响因子:
4.4
通讯作者:
Bacsi, Attila
Bacsi, Attila
中科院分区:
医学2区
文献类型:
--
作者:
Csillag, Aniko;Boldogh, Istvan;Bacsi, Attila

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已经证明花粉粒含有NAD(P)H氧化酶,其在气道中诱导氧化应激,并且这种氧化损伤对于致敏小鼠中过敏性炎症的发展至关重要。在此观察的基础上,我们研究了花粉粒暴露是否会引发树突状细胞(DC)的氧化应激,改变其功能。为了验证这一假设,用豚草花粉粒处理人单核细胞来源的DC。我们的研究结果表明,暴露于花粉粒诱导的活性氧在树突状细胞的细胞内水平增加。我们的数据还表明,除了NAD(P)H氧化酶,花粉粒的其他成分(S)有助于这一现象。细胞内活性氧水平的升高触发了IL-8以及促炎细胞因子如TNF-α和IL-6的产生。用花粉粒处理启动了DC的成熟,强烈上调了CD 80、CD 86、CD 83和HLA-DR的膜表达,并且仅引起了CD 40表达的轻微增加。花粉处理的DC诱导幼稚T淋巴细胞向效应T细胞的发展,具有细胞因子产生的混合概况。抗氧化剂抑制了DCs的表型和功能变化,强调了氧化应激在这些过程中的重要性。总的来说,这些数据表明,花粉萌发诱导的氧化应激可能有助于局部先天免疫,并参与启动适应性免疫反应的花粉抗原。免疫学杂志,2010,184:2377-2385。
It has been demonstrated that pollen grains contain NAD(P)H oxidases that induce oxidative stress in the airways, and this oxidative insult is critical for the development of allergic inflammation in sensitized mice. On the basis of this observation, we have examined whether pollen grain exposure triggers oxidative stress in dendritic cells (DCs), altering their functions. To test this hypothesis, human monocyte-derived DCs were treated with ragweed pollen grains. Our findings show that exposure to pollen grains induces an increase in the intracellular levels of reactive oxygen species in DCs. Our data also indicate that besides the NAD(P)H oxidases, other component(s) of pollen grains contributes to this phenomenon. Elevated levels of intracellular reactive oxygen species triggered the production of IL-8 as well as proinflammatory cytokines, such as TNF-alpha and IL-6. Treatment with pollen grains initiated the maturation of DCs, strongly upregulated the membrane expression of CD80, CD86, CD83, and HLA-DR, and caused only a slight increase in the expression of CD40. The pollen-treated DCs induced the development of naive T lymphocytes toward effector T cells with a mixed profile of cytokine production. Antioxidant inhibited both the phenotypic and functional changes of DCs, underlining the importance of oxidative stress in these processes. Collectively, these data show that pollen exposure-induced oxidative stress may contribute to local innate immunity and participate in the initiation of adaptive immune responses to pollen Ags. The Journal of Immunology, 2010, 184: 2377-2385.