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The cutaneous biochemical redox barrier: a component of the innate immune defences against sensitisation by highly reactive environmental xenobiotics

The cutaneous biochemical redox barrier: a component of the innate immune defences against sensitisation by highly reactive environmental xenobiotics
The cutaneous biochemical redox barrier: a component of the innate immune defences against sensitisation by highly reactive environmental xenobiotics
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.
7576-7584
Pickard, C.
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Louafi, F.
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McGuire, C.
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Lowings, K.
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Kumar, P.
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Cooper, H.
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Dearman, R.J.
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Cumberbatch, M.
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Kimber, I.
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Healy, E.
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Friedmann, P.S.
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Pickard, C.
e21117b3-6345-4d09-a876-ac9965ec4d6a
Louafi, F.
2707157a-9fe8-477b-b79f-6e7724638d6c
McGuire, C.
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Lowings, K.
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Kumar, P.
f57e4ef2-18e6-4f90-be71-7450c42df258
Cooper, H.
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Dearman, R.J.
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Cumberbatch, M.
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Kimber, I.
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Healy, E.
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Friedmann, P.S.
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Pickard, C., Louafi, F., McGuire, C., Lowings, K., Kumar, P., Cooper, H., Dearman, R.J., Cumberbatch, M., Kimber, I., Healy, E. and Friedmann, P.S. (2009) The cutaneous biochemical redox barrier: a component of the innate immune defences against sensitisation by highly reactive environmental xenobiotics. The Journal of Immunology, 183, 7576-7584. (doi:10.4049/jimmunol.0901064).

Record type: Article

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.

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Published date: 2009

Identifiers

Local EPrints ID: 73117
URI: http://eprints.soton.ac.uk/id/eprint/73117
PURE UUID: 5ceb5b22-2f84-4276-ba45-037012784290

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Date deposited: 02 Mar 2010
Last modified: 13 Mar 2024 21:54

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Contributors

Author: C. Pickard
Author: F. Louafi
Author: C. McGuire
Author: K. Lowings
Author: P. Kumar
Author: H. Cooper
Author: R.J. Dearman
Author: M. Cumberbatch
Author: I. Kimber
Author: E. Healy
Author: P.S. Friedmann

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