NDLI: The cutaneous biochemical redox barrier: a component of the innate immune defenses against sensitization by highly reactive environmental xenobiotics.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Cooper, Hywel Lowings, Kelly Friedmann, Peter S. Dearman, Rebecca J. Pickard, Chris McGuire, Carolann Kumar, Pawan Healy, Eugene Louafi, Fethi Cumberbatch, Marie Kimber, Ian
Description	Country affiliation: United kingdom Author Affiliation: Pickard C ( Dermatopharmacology Unit, School of Medicine, Level F South Block (825), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. cp@soton.ac.uk)
Abstract	Contact allergy to environmental xenobiotics is a common and important problem, but it is unclear why some chemicals are potent sensitizers and others weak/nonsensitizers. We explored this by investigating why similar chemicals, 2,4-dinitrochlorobenzene (DNCB) and 2,4-dinitrothiocyanobenzene (DNTB), differ in their ability to induce contact hypersensitivity (CHS). DNCB induced CHS in humans, whereas at similar doses DNTB did not. However, following DNCB sensitization, DNTB elicited CHS in vivo and stimulated DNCB-responsive T cells in vitro, suggesting that differences in response to these compounds lie in the sensitization phase. In contrast to DNCB, DNTB failed to induce emigration of epidermal Langerhans cells in naive individuals. Examination for protein dinitrophenylation in skin revealed that DNCB penetrated into the epidermis, whereas DNTB remained bound to a thiol-rich band within the stratum corneum. DNTB reacted rapidly with reduced glutathione in vitro and was associated with a decrease in the free thiol layer in the stratum corneum, but not in the nucleated epidermis. By contrast, DNCB required GST facilitation to react with gluthathione and, following penetration through the stratum corneum, depleted thiols in the viable epidermis. Chemical depletion of the thiol-rich band or removing it by tape stripping allowed increased penetration of DNTB into the epidermis. Our results suggest that the dissimilar sensitizing potencies of DNCB and DNTB in humans are determined by a previously undescribed outer epidermal biochemical redox barrier, a chemical component of the innate immune defense mechanisms that defend against sensitization by highly reactive environmental chemicals.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	11
Volume Number	183
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2009-12-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Dermatitis, Contact Immunology Dinitrobenzenes Dinitrochlorobenzene Skin Chemistry Xenobiotics Pharmacology Environmental Exposure Immunity, Innate Irritants Keratinocytes Drug Effects Oxidation-reduction Reverse Transcriptase Polymerase Chain Reaction Skin Tests Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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