OPTIMIZATION OF THE MOUSE EAR SWELLING TEST FOR IN-VIVO AND IN-VITRO STUDIES OF WEAK CONTACT SENSITIZERS

OPTIMIZATION OF THE MOUSE EAR SWELLING TEST FOR IN-VIVO AND IN-VITRO STUDIES OF WEAK CONTACT SENSITIZERS
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DOI:
10.1111/j.1600-0536.1994.tb00650.x
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发表时间:
1994-04-01
期刊:
影响因子:
5.5
通讯作者:
SCHMITT, D
SCHMITT, D
中科院分区:
医学2区
文献类型:
--
作者:
GARRIGUE, JL;NICOLAS, JF;SCHMITT, D

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用于评估化学品接触致敏特性的小鼠模型依赖于小鼠耳肿胀试验(Mest),该试验灵敏度不足以检测弱致敏剂。本研究的目的是在小鼠中开发一种不含致敏剂的Mest,适用于体内检测任何类型的致敏剂(从弱到强),并可用于体外评估接触敏感性(CS)。检测了3种半抗原:二硝基氯苯(DNCB)、对苯二胺(PPD)和异丁香酚。我们比较了诱导CS反应的各种方案,不同的是诱导位点、应用次数和3种半抗原的浓度。最佳CS反应的诱导部位的比较表明,在Balb/c小鼠中,背部是比腹部更好的诱导部位。弱致敏剂(PPD,异丁香酚)的致敏特性的检测是可能的,使用一个无促敏剂的协议,只要诱导阶段包括半抗原应用在动物的背部连续3天。对于DNCB,一次应用足以获得最佳CS反应。对于所有3种半抗原,使用来自5天前用优化的Mest致敏的动物的半纯化淋巴结T细胞获得体外二次应答。这些结果表明,Mest可能是一个有用的实验模型的研究,所有类型的接触敏化剂。
Murine models for the assessment of the contact sensitizing properties of chemicals rely on mouse ear swelling tests (Mest), which are not sensitive enough to detect weak sensitizers. The aim of the present study was to develop in mice an adjuvant-free Mest appropriate for in vivo detection of any type of sensitizer (weak to strong), and useful for in vitro assessment of contact sensitivity (CS). 3 haptens were tested: dinitrochlorobenzene (DNCB), para-phenylenediamine (pPD) and isoeugenol. We compared various protocols for induction of the CS reaction, differing by the site of induction, the number of applications and the concentrations of the 3 haptens. Comparison of the induction site for optimal CS reaction showed that, in Balb/c mice, the back was a better site of induction than the abdomen. Detection of the sensitizing properties of weak sensitizers (pPD, isoeugenol) was possible using an adjuvant-free protocol, provided that the induction phase comprised hapten applications on 3 consecutive days on the backs of animals. For DNCB, one application was sufficient to obtain optimal CS reaction. For all 3 haptens, a secondary response in vitro was obtained using semi-purified lymph node T cells from animals sensitized 5 days before with the optimized Mest. These results demonstrate that the Mest could be a useful experimental model for the study of all types of contact sensitizers.