Langerhans cells and immature dendritic cells as model systems for screening of skin sensitizers.
Langerhans cells are the most potent antigen-presenting cells in the skin and play a critical role in the induction of contact allergy. Research on the phenotypical and functional changes of LCs occurring after application of skin sensitizers indicated their use as an in vitro model for the screening of chemicals. In the present investigations, LCs from human skin explants served as the test system. The application of this cell system has been aggravated by the difficulty in isolating sufficient numbers of live LCs from skin. This disadvantage was overcome by the culture of immature dendritic cells from peripheral mononuclear blood cells. These cells can serve as a replacement for LCs as they bind haptens and show phenotypical and functional changes similar to LCs. The sensitizers NiSO(4), dinitrochlorobenzene, 2,4,6-trinitrobenzene sulfonic acid, alpha-hexylcinnamaldehyde and eugenol were applied. Both the expression of surface markers and the induction of intracellular interleukin-1 beta (IL-1 beta) were analyzed. No clear-cut results could be established for intracellular cytokine production, only NiSO(4) induced a remarkable number of IL-1 beta-positive cells. However, all skin sensitizers caused an up-regulation of the co-stimulatory molecule CD86, of intercellular adhesion molecule CD54 and of the HLA-DR antigen. The irritant sodium dodecyl sulfate (SDS) and the vehicle dimethyl sulfoxide (DMSO) had no effect.
Tuschl
H
H
Austrian Research Centers Seibersdorf, Department of Toxicology, A-2444 Seibersdorf, Austria. helga.tuschl@arcs.ac.at
Kovac
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R
D000171:Acrolein / Q000031:analogs & derivatives* / Q000633:toxicity; D000485:Allergens / Q000633:toxicity*; D000826:Animal Testing Alternatives; D015703:Antigens, CD / Q000378:metabolism; D000954:Antigens, Surface / Q000096:biosynthesis; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004137:Dinitrochlorobenzene / Q000633:toxicity; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005054:Eugenol / Q000633:toxicity; D005434:Flow Cytometry; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D007801:Langerhans Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D009532:Nickel / Q000633:toxicity; D012867:Skin; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D015854:Up-Regulation
D000485:Allergens; D015703:Antigens, CD; D000954:Antigens, Surface; D051940:B7-2 Antigen; C497964:CD86 protein, human; D004137:Dinitrochlorobenzene; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D005054:Eugenol; C029938:nickel sulfate; D000171:Acrolein; D009532:Nickel; D014302:Trinitrobenzenesulfonic Acid; C012843:cinnamaldehyde