Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate
Effects of phthalate esters on the sensitization phase of contact hypersensitivity induced by fluorescein isothiocyanate
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DOI：
10.1111/j.1365-2222.2006.02574.x
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发表时间：
2006-11-01
影响因子：
6.1
通讯作者：
Kurohane, K.
中科院分区：
文献类型：
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作者：
Imai, Y.;Kondo, A.;Kurohane, K.
背景许多不同类型的邻苯二甲酸酯被用作增塑剂，因此存在于空气中。有几项研究表明过敏和邻苯二甲酸酯之间存在关联。我们先前发现邻苯二甲酸二丁酯（DBP）在小鼠接触性超敏反应模型中具有佐剂作用，目的研究其他邻苯二甲酸酯是否通过促进异硫氰酸荧光素（FITC）的运输而增强对FITC的致敏作用。将树突状细胞或巨噬细胞从皮肤部位呈递到引流淋巴结。用FITC激发后，将致敏性评价为耳肿胀。通过流式细胞术检测皮肤致敏后24小时获得的引流淋巴结细胞的FITC荧光。结果用含DBP或DPP的丙酮溶液致敏小鼠后，小鼠耳肿胀反应明显增强，且与对照组相比，差异有显著性（P < 0. 05）。邻苯二甲酸二甲酯（DMP）和邻苯二甲酸二乙酯（DEP）的效果较差，但产生了一定的增强作用。用邻苯二甲酸二（2-乙基己基）酯或邻苯二甲酸二异壬酯未观察到一致的增强。DBP或DPP致敏后，引流淋巴结中FITC阳性树突状细胞（总CD11c（+）以及CD11c（+）/CD11b（+））数量增加。至于其他四个邻苯二甲酸酯，有没有显着增加的FITC阳性细胞数在引流lymph nods.Conclusion过程中的致敏FITC，DBP，DPP发挥较强的佐剂作用，这是与增强运输抗原呈递树突状细胞从皮肤引流lymph nods。
Background Many different types of phthalate ester are used as plasticizers and are thus found in the air. There have been several studies that suggest an association between allergies and phthalate esters. We previously found that di-butyl phthalate (DBP) has an adjuvant effect in a mouse contact hypersensitivity model, in which fluorescein isothiocyanate (FITC) is involved as an immunogenic hapten.Objective We examined whether other phthalate esters enhance the process of sensitization to FITC by facilitating the trafficking of FITC-presenting dendritic cells or macrophages from skin sites to draining lymph nodes.Methods Mice were epicutaneously sensitized with FITC dissolved in acetone containing a phthalate ester. Sensitization was evaluated as ear swelling after a challenge with FITC. Draining lymph node cells obtained 24 h after skin sensitization were examined for FITC fluorescence by means of flow cytometry. FITC-positive cells were characterized with anti-CD11c and anti-CD11b by three-colour flow cytometry.Results When mice were sensitized with FITC in acetone containing DBP or di-n-propyl phthalate (DPP), strong enhancement of the ear-swelling response was observed. Di-methyl phthalate (DMP) and di-ethyl phthalate (DEP) were less effective but produced some enhancement. Consistent enhancement was not observed with di-(2-ethylhexyl) phthalate or di- isononyl phthalate. Upon sensitization in the presence of DBP or DPP, the number of FITC-positive dendritic cells (total CD11c(+) as well as CD11c(+)/CD11b(+)) was increased in draining lymph nodes. As to the other four phthalate esters, there was no significant increase in the FITC-positive cell number in the draining lymph nodes.Conclusion During the process of sensitization to FITC, DBP, and DPP exert strong adjuvant effects that are associated with enhancement of trafficking of antigen-presenting dendritic cells from the skin to draining lymph nodes.