Ryan Cindy A, Gerberick G Frank, Gildea Lucy A, Hulette Ben C, Betts Catherine J, Cumberbatch Marie, Dearman Rebecca J, Kimber Ian
Miami Valley Innovation Center, Central Product Safety Department, The Procter & Gamble Company, Cincinnati, Ohio 45253-8707, USA.
Toxicol Sci. 2005 Nov;88(1):4-11. doi: 10.1093/toxsci/kfi245. Epub 2005 Jul 13.
The identification of potential skin sensitizing chemicals is a key step in the overall skin safety risk assessment process. Traditionally, predictive testing has been conducted in guinea pigs. More recently, the murine local lymph node assay (LLNA) has become the preferred test method for assessing skin sensitization potential. However, even with the significant animal welfare benefits provided by the LLNA, there is a need to develop non-animal test methods for skin sensitization. Mechanistic understanding of allergic contact dermatitis has increased substantially in recent years. For example, a number of changes are known to occur in epidermal Langerhans cells, the principal antigen-presenting dendritic cell in the skin, as a result of exposure to chemical allergens, including the internalization of surface major histocompatibility complex (MHC) class II molecules via endocytosis, the induction of tyrosine phosphorylation, the modulation of cell surface markers, and cytokine expression. The application of this knowledge to the design of predictive in vitro alternative tests provides both unique opportunities and challenges. In this review, we have focused specifically on the impact of chemical exposure on dendritic cells and the potential use of that information in the development of cell-based assays for assessing skin sensitization potential of chemicals in vitro.
识别潜在的皮肤致敏化学物质是整个皮肤安全风险评估过程中的关键一步。传统上，预测性测试是在豚鼠身上进行的。最近，小鼠局部淋巴结试验（LLNA）已成为评估皮肤致敏潜力的首选测试方法。然而，即使LLNA带来了显著的动物福利益处，仍有必要开发用于皮肤致敏的非动物测试方法。近年来，对过敏性接触性皮炎的机制理解有了大幅提高。例如，已知由于接触化学过敏原，皮肤中主要的抗原呈递树突状细胞——表皮朗格汉斯细胞会发生许多变化，包括通过内吞作用使表面主要组织相容性复合体（MHC）II类分子内化、酪氨酸磷酸化的诱导、细胞表面标志物的调节以及细胞因子表达。将这些知识应用于预测性体外替代试验的设计既带来了独特的机遇，也带来了挑战。在本综述中，我们特别关注了化学物质暴露对树突状细胞的影响以及该信息在开发基于细胞的试验以体外评估化学物质皮肤致敏潜力方面的潜在用途。
