The expression of surface markers on dendritic cells as indicators for the sensitizing potential of chemicals.
Novel approaches to testing of skin sensitizing chemicals have made use of immature dendritic cells (DCs) cultured from different hematopoietic progenitors. These cells resemble Langerhans cells (LCs), which are the most potent antigen presenting cells in the skin. Former research has focused on the phenotypic and functional changes of LCs after application of skin sensitizers. But it has proven difficult to isolate sufficient numbers of LCs from skin. This disadvantage is overcome by cultures of immature DCs providing high numbers of reactive cells. The aim of the present investigation was to test the response of DC cultures established from different blood donors to known sensitizers, an irritant and a vehicle. The sensitizers NiSO(4), dinitrochlorobenzene (DNCB), 2,4,6 trinitrobenzene sulfonic acid (TNBS), alpha-hexylcinnamaldehyde (Cinn) and eugenol (Eu) induced the 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. A high rate of responders within blood donors was found for NiSO(4), TNBS, Cinn and Eu, while DNCB was less effective. The augmentation of surface marker expression in dendritic cells obtained from peripheral human blood seems to be a promising readout in prescreening for strong and moderate sensitizers. This test could thus help to reduce animal numbers for in vivo testing.
Tuschl
H
H
Austrian Research Centers Seibersdorf, Dept of Toxicology, A-2444, Seibersdorf, Austria. helga.tuschl@arcs.ac.at
Kovac
R
R
Weber
E
E
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000485:Allergens / Q000494:pharmacology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology*; D051940:B7-2 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005054:Eugenol / Q000494:pharmacology; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D015854:Up-Regulation
D000485:Allergens; D015703:Antigens, CD; D000954:Antigens, Surface; D051940:B7-2 Antigen; C497964:CD86 protein, human; D004137:Dinitrochlorobenzene; D006684:HLA-DR Antigens; D007375:Interleukin-1; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D012967:Sodium Dodecyl Sulfate; D005054:Eugenol; C029938:nickel sulfate; D000171:Acrolein; D009532:Nickel; D014302:Trinitrobenzenesulfonic Acid; C012843:cinnamaldehyde; D004121:Dimethyl Sulfoxide