title: The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis.
abstract: Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and hair follicles. We previously proposed a new theory that vitiligo involves the chronic detachment and transepidermal loss of melanocytes caused by autoimmune, neural and impaired redox mechanisms associated with mechanical trauma. In this study, we reconstructed epidermis on dead de-epidermized dermis with normal and/or non-segmental non-lesional vitiligo (NSV) cells and tested catecholamines or sera or hydrogen peroxide. Under unstressed conditions, the number of melanocytes located in the basal layer was significantly lower in reconstructs made with melanocytes from non-lesional NSV skin and normal keratinocytes compared with controls made with autologous normal melanocytes. The number of non-lesional NSV melanocytes was even lower in reconstructs made with keratinocytes from non-lesional NSV skin. Epinephrine and H(2)O(2) could trigger the transepidermal loss of normal and vitiligo melanocytes. Some sera induced melanocyte detachment but without any clear correlation with disease activity in the donors. In conclusion, our results are the first step to obtaining a reproducible melanocytorrhagic model in vitro with some of the stressors investigated. They support the hypothesis that NSV melanocytes have an intrinsic defect, which limits their adhesion in a reconstructed epidermis, with an enhancer effect of the vitiligo keratinocyte milieu.
authors.affiliation: Department of Dermatology, National reference center for rare skin disease, Bordeaux University Hospitals, Bordeaux Cedex, France. muriel.cario-andre@dermatol.u-bordeaux2.fr
authors.forename: M
authors.initials: M
authors.lastname: Cario-André
authors.forename: C
authors.initials: C
authors.lastname: Pain
authors.forename: Y
authors.initials: Y
authors.lastname: Gauthier
authors.forename: A
authors.initials: A
authors.lastname: Taïeb
mesh_terms: D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism; D008954:Models, Biological; D008962:Models, Theoretical; D010858:Pigmentation; D012867:Skin / Q000378:metabolism; D012880:Skin Pigmentation; D013997:Time Factors; D014820:Vitiligo / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006861:Hydrogen Peroxide; D004837:Epinephrine