Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride
Autoimmune response in MRL+/+ mice following treatment with dichloroacetyl chloride or dichloroacetic anhydride
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DOI：
10.1016/j.taap.2006.05.010
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发表时间：
2006-10-15
影响因子：
3.8
通讯作者：
Ansari, G. A. S.
中科院分区：
文献类型：
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作者：
Cai, Ping;Konig, Rolf;Ansari, G. A. S.
二氯乙酰氯（DCAC）是由三氯乙烯（TCE）形成的，其涉及诱导/加速自身免疫反应。由于其强大的酰化活性，DCAC可以将蛋白质转化为新抗原，从而可以诱导自身免疫反应。二氯乙酸酐（DCAA），这是一个类似的酰化剂，也可能诱导自身免疫反应。为了评估氯酰化是否在诱导自身免疫中起作用，我们测量了用DCAC或DCAA治疗自身免疫易感MRL +/+小鼠后的自身免疫应答。5周龄雌性小鼠腹腔内注射（每周两次）0.2 mmol/kg DCAC或DCAA玉米油溶液，持续6周。与对照组相比，DCAC治疗组小鼠的血清总IgG、IgG 1和IgE水平显著升高。这些增加与DCAC特异性IgG和IgG 1水平的增加相对应。DCAC和DCAA处理的小鼠血清总IgM均降低。抗核抗体，作为全身性自身免疫反应的指标，在DCAC和DCAA治疗的小鼠中均增加。在血清中测量的8种Th 1/Th 2细胞因子中，两个治疗组中仅IL-5显著降低。治疗组和对照组之间，用抗CD 3（T细胞受体介导的信号）和CD 28（共刺激信号）抗体刺激后脾淋巴细胞的细胞因子分泌模式不同。IL-1，IL-3，IL-6，IFN-γ，G-CSF和KC的水平在DCAC或DCAA处理小鼠的刺激脾细胞培养物中高于对照组。IL-17的水平仅在来自DCAC处理的小鼠的培养物中增加。用DCAC或DCAA处理后，在脾脏红髓中发现淋巴细胞群增加。此外，观察到DCAC或DCAA处理的小鼠的肺中的肺泡隔增厚。暴露小鼠的肺组织病理学与暴露于DCAC/光气的焊工的肺组织病理学一致。在DCAC处理的小鼠中增厚更明显。我们的数据表明，DCAC和DCAA引起MRL+/+小鼠的自身免疫反应，这可能反映了它们在体内的氯酰化潜力。(c)2006年爱思唯尔公司All rights reserved.
Dichloroacetyl chloride (DCAC) is formed from trichloroethene (TCE), which is implicated in inducing/accelerating autoimmune response. Due to its potent acylating activity, DCAC may convert proteins to neo-antigens and thus could induce autoimmune responses. Dichloroacetic anhydride (DCAA), which is a similar acylating agent, might also induce autoimmune responses. To evaluate if chloroacylation plays a role in the induction of autoimmunity, we have measured the autoimmune responses following treatment with DCAC or DCAA in autoimmune-prone MRL +/+ mice. Five-week-old female mice were injected intraperitoneally (twice weekly) with 0.2 mmol/kg of DCAC or DCAA in corn oil for 6 weeks. Total serum IgG, IgG1, and IgE levels were significantly increased in DCAC-treated mice as compared to controls. These increases corresponded with increases in DCAC-specific IgG and IgG1 levels. Total serum IgM was decreased in both DCAC- and DCAA-treated mice. Antinuclear antibodies, measured as an indication of systemic autoimmune responses, were increased in both DCAC- and DCAA-treated mice. Of eight Th1/Th2 cytokines measured in the serum, only IL-5 was significantly decreased in both treatment groups. The cytokine secretion patterns of splenic lymphocytes after stimulation with antibodies against CD3 (T cell receptor-mediated signal) and CD28 (costimulatory signal) differed between treatment and control groups. Levels of IL-1, IL-3, IL-6, IFN-gamma, G-CSF, and KC were higher in cultures of stimulated splenocytes from either DCAC- or DCAA-treated mice than from controls. The level of IL-17 was only increased in cultures from DCAC-treated mice. Increased lymphocytic populations were found in the red pulp of spleens following treatment with either DCAC or DCAA. In addition, thickening of the alveolar septa in the lungs of DCAC- or DCAA-treated mice was observed. The lung histopathology in exposed mice was consistent with the symptomology observed in welders exposed to DCAC/phosgene. Thickening was more pronounced in DCAC-treated mice. Our data suggest that DCAC and DCAA elicit autoimmune responses in MRL+/+ mice that might be reflective of their chloroacylation potential in vivo. (c) 2006 Elsevier Inc. All rights reserved.