Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice
Differential immune responses to albumin adducts of reactive intermediates of trichloroethene in MRL+/+ mice
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DOI：
10.1016/j.taap.2007.01.020
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发表时间：
2007-05-01
影响因子：
3.8
通讯作者：
Ansari, G. A. S.
中科院分区：
文献类型：
--
作者：
Cai, Ping;Konig, Rolf;Ansari, G. A. S.
三氯乙烯（TCE）是一种工业脱脂溶剂和广泛的环境污染物。接触 TCE 与自身免疫有关。 TCE 的作用方式是通过其氧化代谢，最有可能的是，免疫毒性是通过大分子的半抗原化和随后诱导的免疫反应介导的。为了更好地了解蛋白质半抗原化通过 TCE 代谢的作用，我们用各种 TCE 反应中间体的白蛋白加合物对 MRL+/+ 小鼠进行免疫。测量血清免疫球蛋白和细胞因子水平以确定针对半抗原化白蛋白的免疫反应。我们发现 IgG 亚型 IgG(1)、IgG(2a) 和 TgG(2b) 的抗原特异性 IgG 反应，其中 IgG 占主导地位。免疫小鼠的血清 G-CSF 水平升高，表明巨噬细胞被激活。肝脏组织学显示在用甲酰白蛋白免疫后小叶和汇管区有淋巴细胞浸润。我们的研究结果表明，TCE 代谢物半抗原化的蛋白质可能作为新抗原，诱导体液免疫反应和 T 细胞介导的肝炎。 (c) 2007 Elsevier Inc. 保留所有权利。
Trichloroethene (TCE) is an industrial degreasing solvent and widespread environmental contaminant. Exposure to TCE is associated with autoimmunity. The mode of action of TCE is via its oxidative metabolism, and most likely, immunotoxicity is mediated via haptenization of macromolecules and subsequent induction of immune responses. To better understand the role of protein haptenization through TCE metabolism, we immunized MRL+/+ mice with albumin adducts of various TCE reactive intermediates. Serum immunoglobulins and cytokine levels were measured to determine immune responses against haptenized albumin. We found antigen-specific IgG responses of the IgG subtypes IgG(1), IgG(2a), and TgG(2b), with IgG, predominating. Serum levels of G-CSF were increased in immunized mice, suggesting macrophage activation. Liver histology revealed lymphocyte infiltration in the lobules and the portal area following immunization with formyl-albumin. Our findings suggest that proteins haptenized by metabolites of TCE may act as neo-antigens that can induce humoral immune responses and T cell-mediated hepatitis. (c) 2007 Elsevier Inc. All rights reserved.