Metabolic requirements for induction of contact hypersensitivity to immunotoxic polyaromatic hydrocarbons.
Experiments were performed to define the metabolic requirements for induction of contact hypersensitivity to polyaromatic hydrocarbons (PAHs), environmental xenobiotics that are both immunotoxic and carcinogenic. Evidence that conversion of the parent compound to a reactive metabolite was necessary for the development of contact hypersensitivity included the fact 1) that contact hypersensitivity to the polyaromatic hydrocarbon dimethylbenz(a)anthracene (DMBA) only occurred in strains of mice that could metabolize the compound, 2) that among the PAHs, only those that could induce aryl hydrocarbon hydroxylase, the rate-limiting enzyme in the PAH metabolic pathway, were immunogenic, and 3) that inhibitors of PAH metabolism reduced DMBA contact hypersensitivity. Cells from the XS52 Langerhans cell-like dendritic cell line were able to metabolize the PAH benzo(a)pyrene to its diol, quinone, and phenol metabolites. GM-CSF augmented benzo(a)pyrene metabolism in XS52 cells. Finally, in vivo depletion of CD8+, but not CD4+, T cell populations inhibited contact hypersensitivity to DMBA. The implications of these experiments are that at least for some contact allergens, the metabolic status of the host is a key determinant of individual susceptibility to the development of allergic contact dermatitis, and the metabolic pathway of an individual hapten may have ramifications for the T cell subpopulation-CD4 or CD8-that is activated.
Anderson
C
C
Department of Dermatology, Case Western Reserve University, University Hospitals of Cleveland, Ohio 44106, USA.
Hehr
A
A
Robbins
R
R
Hasan
R
R
Athar
M
M
Mukhtar
H
H
Elmets
C A
CA
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology*; D004817:Epidermis / Q000276:immunology*; D051379:Mice; D011083:Polycyclic Compounds / Q000276:immunology* / Q000378:metabolism / Q000633:toxicity
D011083:Polycyclic Compounds