Responsiveness of human monocyte-derived dendritic cells to thimerosal and mercury derivatives.
Several cases of skin sensitization have been reported following the application of thimerosal, which is composed of ethyl mercury and thiosalicylic acid (TSA). However, few in vitro studies have been carried out on human dendritic cells (DCs) which play an essential role in the initiation of allergic contact dermatitis. The aim of the present study was to identify the effect of thimerosal and other mercury compounds on human DCs. To address this purpose, DCs derived from monocytes (mono-DCs) were used. Data show that thimerosal and mercury derivatives induced DC activation, as monitored by CD86 and HLA-DR overexpression associated with the secretion of tumor necrosis factor alpha and interleukin 8, similarly to lipopolysaccharide and the sensitizers, 1-chloro-2,4-dinitrobenzene (DNCB) and nickel sulfate, which were used as positive controls. In contrast, TSA, the non-mercury part of thimerosal, as well as dichloronitrobenzene, a DNCB negative control, and the irritant, sodium dodecyl sulfate, had no effect. Moreover, oxidative stress, monitored by ROS induction and depolarization of the mitochondrial membrane potential, was induced by thimerosal and mercury compounds, as well as DNCB, in comparison with hydrogen peroxide, used as a positive control. The role of thiol oxidation in the initiation of mono-DC activation was confirmed by a pre-treatment with N-acetyl-l-cysteine which strongly decreased chemical-induced CD86 overexpression. These data are in agreement with several clinical observations of the high relevance of thimerosal in patch-test reactions and prove that human mono-DCs are useful in vitro tools for determining the allergenic potency of chemicals.
Migdal
C
C
Université Lyon 1, EA 41-69, Laboratoire de Recherche Dermatologique, Pavillon R, Hôpital Edouard Herriot, Lyon, France.
Tailhardat
M
M
Courtellemont
P
P
Haftek
M
M
Serres
M
M
D051940:B7-2 Antigen / Q000096:biosynthesis; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017669:Mercury Compounds / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis; D013849:Thimerosal / Q000494:pharmacology*
D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D017669:Mercury Compounds; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D013849:Thimerosal