Title
Subtoxic concentrations of allergenic haptens induce LC migration and maturation in a human organotypic skin explant culture model: A novel method for identifying potential contact allergens
Author
Lehé, C.L.
Jacobs, J.J.L.
Hua, C.M.
Courtellemont, P.
Elliott, G.R.
Das, P.K.
TNO Defensie en Veiligheid
Publication year
2006
Abstract
The accelerated migration of Langerhans cells (LCs) out of the epidermis and up-regulation of maturation markers, upon treatment with subtoxic concentrations of chemicals, were used as the criteria to determine the potential of allergenic chemicals capable of inducing a hapten-specific delayed-type hypersensitivity reaction. Here we report the findings of a study in which seven chemicals, coded and tested in a blind fashion, were classified as contact allergens or non-allergens using the human organotypic skin explant culture (hOSEC) model. All chemicals that were identified as a contact sensitizer on decoding induced a definite decrease in the number of CD1a and HLA-DR-positive epidermal LCs in the epidermis of the skin explants, as determined by both semiquantitative immunohistochemistry and quantitative flow cytometric analysis. A significant increase in the number of CD83+ cells was accompanied by up-regulation of activation molecules in the epidermis of hOSEC exposed specifically to contact allergens. In contrast, there were only minor alterations in epidermal LC numbers, expression of CD83 and other activation markers by LCs when the biopsies were treated with non-toxic concentrations of non-allergenic irritants and vehicles. The data suggest that an increased epidermal LC migration and maturation accompanied by increased expression of activation markers could be used as end-point determinants to screen allergens in a non-animal alternative hOSEC model. © Blackwell Munksgaard, 2006.
Subject
Activation markers
Allergen
HOSEC
Langerhans cell
Migration
CD83 antigen
Contact allergen
Hapten
HLA DR antigen
Irritant agent
T6 antigen
Allergenicity
Antigen expression
Article
Cell maturation
Cell migration
Controlled study
Delayed hypersensitivity
Epidermis
Epidermis cell
Explant
Flow cytometry
Human
Human tissue
immunohistochemistry
Langerhans cell
Quantitative analysis
Skin biopsy
Skin culture
Upregulation
Allergens
Antigens, CD
Cell Differentiation
Cell Movement
Dermatitis, Allergic Contact
Haptens
Humans
Immunoglobulins
Langerhans Cells
Membrane Glycoproteins
Models, Biological
Skin
Tissue Culture Techniques
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DOI
https://doi.org/10.1111/j.0906-6705.2006.00415.x
TNO identifier
239308
ISSN
0906-6705
Source
Experimental Dermatology, 15 (6), 421-431
Document type
article