Murine bone marrow-derived dendritic cells as a potential in vitro model for predictive identification of chemical sensitizers.
The identification of potential sensitizing chemicals is a key step in the safety assessment process. To this end, predictive tests that require no or few animals and that are reliable, inexpensive and easy to perform are needed. The aim of this study was to evaluate the performance of murine bone marrow-derived dendritic cells (BMDCs) in an in vitro skin sensitization model. BMDCs were exposed to six well-known allergens (dinitrochlorobenzene, DNCB; dinitrofluorobenzene, DNFB; Bandrowski's base, BB; paraphenylenediamine, PPD; nickel sulfate, NiSO(4); cinnamaldehyde, Cinn). Surface expression of MHC class II, CD40, CD54, and CD86 was measured by flow cytometry after 48h exposure to these chemicals. All the allergens tested induced a significant increase in marker expression, with an augmentation in the percentage of mature cells ranging from 2.3- to 10.5-fold change over control. The level of up-regulation was dependent on the concentration and the strength of the allergens. In contrast, the irritants (sodium dodecyl sulfate, SDS and 4-aminobenzoic acid, pABA) and the negative control (zinc sulfate, ZnSO(4)) tested induced either no modification or a down-regulation of membrane marker expression. Taken together, our data suggest that murine BMDCs may represent a new and valuable in vitro model to predict the sensitizing properties of chemicals.
Pépin
Elsa
E
Department of Pollutants and Health, National Institute for Research and Safety, 54501 Vandoeuvre-les-Nancy, France. elsa.pepin@inrs.fr
Goutet
Michèle
M
Ban
Masarin
M
D010129:4-Aminobenzoic Acid / Q000633:toxicity; D000171:Acrolein / Q000031:analogs & derivatives / Q000633:toxicity; D000485:Allergens / Q000633:toxicity*; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004137:Dinitrochlorobenzene / Q000633:toxicity; D004139:Dinitrofluorobenzene / Q000633:toxicity; D007509:Irritants / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D009532:Nickel / Q000633:toxicity; D010655:Phenylenediamines / Q000633:toxicity; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D018675:Toxicity Tests / Q000379:methods*
D000485:Allergens; D000954:Antigens, Surface; D004137:Dinitrochlorobenzene; D007509:Irritants; D008070:Lipopolysaccharides; D010655:Phenylenediamines; D012967:Sodium Dodecyl Sulfate; C029938:nickel sulfate; D000171:Acrolein; D009532:Nickel; D004139:Dinitrofluorobenzene; C012843:cinnamaldehyde; D010129:4-Aminobenzoic Acid; C029728:4-phenylenediamine