PMID- 16014741 OWN - NLM STAT- MEDLINE DCOM- 20051115 LR - 20151119 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 88 IP - 1 DP - 2005 Nov TI - Interactions of contact allergens with dendritic cells: opportunities and challenges for the development of novel approaches to hazard assessment. PG - 4-11 AB - 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. FAU - Ryan, Cindy A AU - Ryan CA AD - Miami Valley Innovation Center, Central Product Safety Department, The Procter & Gamble Company, Cincinnati, Ohio 45253-8707, USA. ryan.ca@pg.com FAU - Gerberick, G Frank AU - Gerberick GF FAU - Gildea, Lucy A AU - Gildea LA FAU - Hulette, Ben C AU - Hulette BC FAU - Betts, Catherine J AU - Betts CJ FAU - Cumberbatch, Marie AU - Cumberbatch M FAU - Dearman, Rebecca J AU - Dearman RJ FAU - Kimber, Ian AU - Kimber I LA - eng PT - Journal Article PT - Review DEP - 20050713 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Allergens) RN - 0 (Biomarkers) RN - 0 (Cytokines) SB - IM MH - Allergens/classification/*toxicity MH - *Animal Testing Alternatives MH - Animals MH - Biomarkers MH - Cells, Cultured MH - Cytokines/metabolism MH - Dermatitis, Allergic Contact/*etiology/immunology MH - Humans MH - Langerhans Cells/*drug effects/immunology/metabolism MH - Risk Assessment RF - 74 EDAT- 2005/07/15 09:00 MHDA- 2005/11/16 09:00 CRDT- 2005/07/15 09:00 PHST- 2005/07/15 09:00 [pubmed] PHST- 2005/11/16 09:00 [medline] PHST- 2005/07/15 09:00 [entrez] AID - kfi245 [pii] AID - 10.1093/toxsci/kfi245 [doi] PST - ppublish SO - Toxicol Sci. 2005 Nov;88(1):4-11. doi: 10.1093/toxsci/kfi245. Epub 2005 Jul 13.