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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on November 15, 2006; DOI: 10.1124/jpet.106.113803

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Received for publication September 12, 2006.
Revised November 13, 2006.
Accepted for publication November 13, 2006.

Activation of human dendritic cells by p-phenylenediamine

Eve M. Coulter 1, John Farrell 1, Karen L. Mathews 1, James L. Maggs 1, Camilla K. Pease 2, David J. Lockley 2, David A. Basketter 2, B. Kevin Park 1, Dean J. Naisbitt 1*

1 The University of Liverpool 2 Unilever Research

* Address correspondence to: E-mail: dnes{at}liv.ac.uk

Abstract

Exposure to p-phenylenediamine (pPD), a primary intermediate in hair dye formulations, is often associated with the development of allergic contact dermatitis. Such reactions involve activation of the subject's immune system. The aim of these studies was to explore the relationship between pPD oxidation and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells were incubated with pPD and Bandrowski's base (BB) for 16 h and expression of the co-stimulatory receptors CD40, CD80, CD83, CD86 and MHC class II, intracellular glutathione levels and cell viability were measured. In certain experiments, glutathione (1mM) was added to culture medium. LC-MS analysis and exhaustive solvent extraction were used to monitor the rate of [14C] pPD oxidation and the extent of pPD binding to cellular and serum protein, respectively. Proliferation of allogeneic lymphocytes was determined by incorporation of [3H]thymidine. Exposure of dendritic cells to pPD (5-50µM), but not BB, was associated with an increase in CD40 and MHC class II expression and proliferation of allogeneic lymphocytes. Dendritic cell activation with pPD was not associated with apoptotic or necrotic cell death, or depletion of glutathione. Neither pPD nor BB altered dendritic cell expression of CD80, CD83 or CD86. LC-MS analysis revealed pPD was rapidly oxidised in cell culture media to BB. Addition of glutathione inhibited BB formation, but did not prevent covalent binding of pPD to dendritic cell protein or dendritic cell activation. Collectively, these studies show that pPD, but not BB, selectively activates human dendritic cells in vitro.


Key words: contact allergy, dendritic cells, hair dye, immunotoxicology, oxidation, p-phenylenediamine


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 Am J EpidemiolHome page
Y. Zhang, S. D. Sanjose, P. M. Bracci, L. M. Morton, R. Wang, P. Brennan, P. Hartge, P. Boffetta, N. Becker, M. Maynadie, et al.
Personal Use of Hair Dye and the Risk of Certain Subtypes of Non-Hodgkin Lymphoma
Am. J. Epidemiol., June 1, 2008; 167(11): 1321 - 1331.
[Abstract] [Full Text] [PDF]


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