Induction of autoimmunity to brain antigens by developmental mercury exposure.
Induction of autoimmunity to brain antigens by developmental mercury exposure.
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通过发育汞暴露诱导对脑抗原的自身免疫。
DOI：
10.1093/toxsci/kfq334
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发表时间：
2011
期刊：
影响因子：
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通讯作者：
Lawrence,DavidA
中科院分区：
文献类型：
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作者：
Zhang,Yubin;Gao,Donghong;Bolivar,ValerieJ;Lawrence,DavidA
A.SW 小鼠已知容易患汞 (Hg) 诱导的免疫性肾炎，我们评估了它们在发育过程中接触汞后对脑抗原产生自身免疫的能力。使用含有亚临床剂量的 1.25μM 甲基汞 (MeHg) 或 50μM 氯化汞 (HgCl2) 的母体饮用水来评估对脑抗原的免疫反应的发育诱导（从妊娠第 8 天到出生后第 21 天的暴露）。仅HgCl2诱导自身抗体产生；暴露于 HgCl2 的后代表现出表达 CD25 和 Vβ8.3 链的 CD4+ 脾 T 细胞数量增加，并且脑反应性免疫球蛋白 G (IgG) 抗体主要针对核蛋白（30 和 34 kD）。抗体沉积在所有大脑区域。尽管暴露于 HgCl2 的雄性和雌性 A.SW 小鼠在多个脑区均显示 IgG 沉积，但仅在雌性 A.SW 小鼠的小脑 (CB) 中观察到炎症反应。这些反应与探索行为水平的增加有关。发育过程中接触甲基汞也会引起 CB 炎症，并增加雌性 A.SW 小鼠的探索行为，但这种变化与大脑中 IgG 的增加无关。有趣的是，在探索性行为评估过程中，未接触汞的雌性 A.SW 小鼠比雄性 A.SW 小鼠更容易习惯（适应新环境的信息和/或刺激），并且汞暴露消除了这种习惯（即后续试验中行为没有变化），使雌性行为更像雄性 A.SW 小鼠。此外，汞暴露之前 A.SW 脑细胞因子表达的性别差异被汞暴露消除了。
A.SW mice, which are known to be prone to mercury (Hg)-induced immune nephritis, were assessed for their ability to develop autoimmunity to brain antigens after developmental exposure to Hg. Maternal drinking water containing subclinical doses of 1.25μM methyl Hg (MeHg) or 50μM Hg chloride (HgCl2) were used to evaluate developmental (exposure from gestational day 8 to postnatal day 21) induction of immune responses to brain antigens. Only HgCl2induced autoantibody production; the HgCl2-exposed offspring showed an increased number of CD4+splenic T cells expressing CD25 and Vβ8.3 chains, and the brain-reactive immunoglobulin G (IgG) antibodies were predominantly against nuclear proteins (30 and 34 kD). The antibodies were deposited in all brain regions. Although male and female A.SW mice exposed to HgCl2showed deposition of IgG in multiple brain regions, inflammation responses were observed only in the cerebellum (CB) of female A.SW mice; these responses were associated with increased levels of exploratory behavior. The developmental exposure to MeHg also induced inflammation in the CB and increased exploratory behavior of the female A.SW mice, but the change did not correlate with increased IgG in the brain. Interestingly, the non–Hg-exposed female A.SW mice habituated (adapted to the information and/or stimuli of a new environment) more than the male A.SW mice during exploratory behavior assessment, and the Hg exposure eliminated the habituation (i.e., no changes in behavior with subsequent trials), making the female behaviors more like those of the male A.SW mice. Additionally, gender differences in A.SW brain cytokine expressions prior to Hg exposure were eliminated by the Hg exposure.