PMID- 15140218 OWN - NLM STAT- MEDLINE DCOM- 20040625 LR - 20171116 IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 122 IP - 5 DP - 2004 May TI - Characterization of the sensitizing potential of chemicals by in vitro analysis of dendritic cell activation and skin penetration. PG - 1154-64 AB - Development of in vitro models to identify sensitizing chemicals receives public interest since animal testing should be avoided whenever possible. In this article we analyze two essential properties of sensitizing chemicals: skin penetration and dendritic cell (DC) activation. Activation of immature DC derived from peripheral blood monocytes was evaluated by flow cytometric analysis of CD86 positive cells and quantitative measurement of interleukin-1beta and aquaporin P3 gene expression. The sensitizer 2,4,6-trinitrobenzenesulfonic acid induced a concentration-dependent response for all parameters, whereas the irritant sodium lauryl sulfate did not. When two related aromatic amines, p-toluylenediamine (PTD) and hydroxyethyl-p-phenylenediamine (HE-PPD) were tested, both induced substantial DC activation indicating their potential sensitizing properties. These findings contrasted with in vivo results: in murine local lymph node assays (LLNA) PTD, but not HE-PPD, was sensitizing using acetone/aqua/olive oil as vehicle. Skin penetration measurement revealed that this was due to bioavailability differences. On retesting HE-PPD in the LLNA using the penetration enhancer dimethylsulfoxide as vehicle, it induced a specific response. We conclude that in vitro analysis of DC activation capability of the two selected chemicals demonstrates that prediction of skin sensitization potential is possible provided that skin penetration data indicate sufficient bioavailability of the test compound. FAU - Aeby, Pierre AU - Aeby P AD - Cosmital SA, (Research company of Wella AG) Marly, Switzerland. paeby@cosmital.ch FAU - Wyss, Christoph AU - Wyss C FAU - Beck, Heinz AU - Beck H FAU - Griem, Peter AU - Griem P FAU - Scheffler, Heike AU - Scheffler H FAU - Goebel, Carsten AU - Goebel C LA - eng PT - Journal Article PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (AQP3 protein, human) RN - 0 (Amines) RN - 0 (Antigens, CD) RN - 0 (Aqp3 protein, mouse) RN - 0 (Aquaporins) RN - 0 (B7-2 Antigen) RN - 0 (CD86 protein, human) RN - 0 (Cd86 protein, mouse) RN - 0 (Interleukin-1) RN - 0 (Irritants) RN - 0 (Membrane Glycoproteins) RN - 158801-98-0 (Aquaporin 3) RN - 207137-56-2 (Interleukin-4) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Amines/pharmacology MH - Animal Testing Alternatives MH - Animals MH - Antigens, CD/analysis MH - Aquaporin 3 MH - Aquaporins/genetics MH - B7-2 Antigen MH - Cell Differentiation/drug effects/immunology MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/*immunology MH - Dermatitis, Allergic Contact/*immunology MH - Female MH - Gene Expression/drug effects MH - Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology MH - Humans MH - In Vitro Techniques MH - Interleukin-1/genetics MH - Interleukin-4/pharmacology MH - Irritants/*pharmacology MH - Membrane Glycoproteins/analysis MH - Mice MH - Mice, Inbred CBA MH - Monocytes/chemistry/cytology/immunology MH - Skin/*immunology MH - Swine EDAT- 2004/05/14 05:00 MHDA- 2004/06/26 05:00 CRDT- 2004/05/14 05:00 PHST- 2004/05/14 05:00 [pubmed] PHST- 2004/06/26 05:00 [medline] PHST- 2004/05/14 05:00 [entrez] AID - S0022-202X(15)30802-2 [pii] AID - 10.1111/j.0022-202X.2004.22402.x [doi] PST - ppublish SO - J Invest Dermatol. 2004 May;122(5):1154-64. doi: 10.1111/j.0022-202X.2004.22402.x.