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首页> 外文期刊>Toxicology and Applied Pharmacology >Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses.
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Lead effects on development and function of bone marrow-derived dendritic cells promote Th2 immune responses.

机译：骨髓源性树突状细胞的发育和功能的先导作用促进Th2免疫反应。

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Although lead (Pb) has significant effects on the development and function of macrophages, B cells, and T cells and has been suggested to promote allergic asthma in mice and humans, Pb modulation of bone marrow (BM)-derived dendritic cells (DCs) and the resultant DC effects on Th1 and Th2 development have not been examined. Accordingly, we cultured BM cells with murine granulocyte macrophage-colony stimulating factor (mGM-CSF)+/-PbCl(2). At day 10, culture supernatant (SN) and non-adherent cells were harvested for analysis. Additionally, day 10 non-adherent BM-DCs were harvested and recultured with mGM-CSF+LPS+/-Pb for 2 days. The day 10 Pb exposure significantly inhibited BM-DC generation, based on CD11c expression. Although fewer DCs were generated with Pb, the existing Pb-exposed DCs had significantly greater MHC-II expression than did the non-Pb-exposed DCs. However, these differences diminished upon LPS stimulation. After LPS stimulation, CD80, CD86, CD40, CD54, and MHC-II were all up-regulated onboth Pb-DCs and DCs, but Pb-DCs expressed significantly less CD80 than did DCs. The CD86:CD80 ratio suggests a Pb-DC potential for Th2 cell development. After LPS stimulation, IL-6, IL-10, IL-12 (p70), and TNF-alpha levels significantly increased with both Pb-DCs and DCs, but Pb-DCs produced significantly less cytokines than did DCs, except for IL-10, which further supports Pb-DC preferential skewing toward type-2 immunity. In vitro studies confirm that Pb-DCs have the ability to polarize antigen-specific T cells to Th2 cells. Pb-DCs also enhanced allogeneic and autologous T cell proliferation in vitro, and in vivo studies suggested that Pb-DCs inhibited Th1 effects on humoral and cell-mediated immunity. The Pb effect was mainly on DCs, rather than on T cells, and Pb's modification of DC function appears to be the main cause of Pb's promotion of type-2-related immunity, which may relate to Pb's enhanced activation of the Erk/MAP kinase pathway.
机译：尽管铅（Pb）对巨噬细胞，B细胞和T细胞的发育和功能有显着影响，并且已被建议促进小鼠和人类的过敏性哮喘，但是铅（Pb调节）骨髓（BM）衍生的树突状细胞（DCs）并且尚未研究由此产生的DC对Th1和Th2发育的影响。因此，我们用鼠粒细胞巨噬细胞集落刺激因子（mGM-CSF）+/- PbCl（2）培养了BM细胞。在第10天，收获培养上清液（SN）和非贴壁细胞用于分析。另外，收获第10天的非粘附BM-DC并用mGM-CSF + LPS +/- Pb再培养2天。根据CD11c表达，第10天暴露于Pb会明显抑制BM-DC的产生。尽管用Pb生成的DC较少，但现有的暴露Pb的DC的MHC-II表达明显高于未暴露Pb的DC。但是，这些差异在LPS刺激后减弱。在LPS刺激之后，CD80，CD86，CD40，CD54和MHC-II在Pb-DC和DC上均被上调，但Pb-DC的CD80明显少于DC。 CD86：CD80比值表明Th2细胞发育具有Pb-DC潜力。 LPS刺激后，Pb-DC和DC均显着增加IL-6，IL-10，IL-12（p70）和TNF-α的水平，但Pb-DC产生的细胞因子明显少于DC，但IL-除外。 10，进一步支持Pb-DC优先偏向2型免疫。体外研究证实，Pb-DC具有将抗原特异性T细胞极化为Th2细胞的能力。 Pb-DC在体外还增强了同种异体和自体T细胞的增殖，体内研究表明Pb-DC抑制了Th1对体液和细胞介导的免疫的作用。 Pb的作用主要是对DC的作用，而不是对T细胞的作用，Pb对DC功能的修饰似乎是Pb促进2型相关免疫的主要原因，这可能与Pb增强的Erk / MAP激酶激活有关。途径。

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