Coutant K D, Ulrich P, Thomas H, Cordier A, Brugerolle de Fraissinette A
Novartis Pharma, Preclinical Safety, Toxicology/Pathology, Basel, Switzerland.
Toxicol Sci. 1999 Mar;48(1):74-81. doi: 10.1093/toxsci/48.1.74.
In order to develop an in vitro predictive assay for the detection of contact sensitizers, we investigated the possible modulation of the expression of cell-surface molecules in the early phases of treatment of murine epidermal cells (EC) with known contact sensitizers. After in vitro treatment of Balb/c EC with the strong contact sensitizer, TNBS, Langerhans cells (LCs) demonstrated a rapid up-regulation of CD45, CD40, CD32/16 (Fc gamma RII/III) and CD23 (Fc epsilon RII) molecules. CD45 and CD40 were also rapidly up-regulated on the dendritic epidermal T cells. Interestingly, after treatment with this severe sensitizer, a marked induction of CD40 expression was found on a CD45 negative population, most probably keratinocytes. In contrast to these cell-surface molecules, I-Ad/I-Ed and CD90.2 expression were unchanged. No change was observed on the expression of CD45 and CD40 after treatment with a mild or a weak contact sensitizer, citral and citronellal respectively. In contrast, like TNBS, they up-regulated the expression of CD32/16 and CD23 on LCs. The irritant sodium dodecyl sulfate had no effect on all these cell-surface molecules. Our results indicated that in vitro, chemicals with allergic potential induced early specific phenotype changes that may represent an early-activated state of the cells. This state may be responsible for initiating the afferent phase of contact sensitivity in vivo. Based on these findings, it might be possible to develop an in vitro assay to reduce the number of experimental animals for a fast screening of contact sensitizers and for discriminating between mild contact sensitizers and irritants.
为了开发一种用于检测接触性致敏剂的体外预测性检测方法，我们研究了用已知接触性致敏剂处理小鼠表皮细胞（EC）早期阶段细胞表面分子表达的可能调节情况。用强接触性致敏剂三硝基苯磺酸（TNBS）对Balb/c EC进行体外处理后，朗格汉斯细胞（LC）显示出CD45、CD40、CD32/16（FcγRII/III）和CD23（FcεRII）分子的快速上调。树突状表皮T细胞上的CD45和CD40也快速上调。有趣的是，在用这种强效致敏剂处理后，在一个CD45阴性群体（很可能是角质形成细胞）上发现了CD40表达的显著诱导。与这些细胞表面分子相反，I-Ad/I-Ed和CD90.2的表达没有变化。用轻度或弱接触性致敏剂柠檬醛和香茅醛处理后，CD45和CD40的表达没有变化。相反，与TNBS一样，它们上调了LC上CD32/16和CD23的表达。刺激性的十二烷基硫酸钠对所有这些细胞表面分子均无影响。我们的结果表明，在体外，具有过敏潜力的化学物质会诱导早期特异性表型变化，这可能代表细胞的早期激活状态。这种状态可能是体内引发接触性敏感传入阶段的原因。基于这些发现，有可能开发一种体外检测方法，以减少用于快速筛选接触性致敏剂以及区分轻度接触性致敏剂和刺激物的实验动物数量。
