Lithraea caustica, or litre, a tree of the Anacardiaceae family that is endemic to the central region of Chile, induces a severe
contact dermatitis in susceptible human beings. The
allergen was previously isolated and characterized as a 3-(pentadecyl-10-enyl)
catechol, a molecule belonging to the
urushiol group of
allergens isolated from poison ivy and poison oak plants. Because urushiols are pro-electrophilic
haptens, it is believed that the reactive species are generated intracellularly by skin keratinocytes and Langerhans cells. The active species are presumed to modify self
proteins which, after proteolytic processing, would generate immunogenic
peptides carrying the
hapten. The presence of a 15-carbon-length hydrophobic chain should impair antigen presentation of self-modified
peptides by class I MHC molecules, either by steric hindrance or by limiting their sorting to the ER lumen. We have proposed that the shortening of the aliphatic chain by beta-oxidation within peroxisomes and/or mitochondria should be a requirement for the antigen presentation process. To test this hypothesis we investigated the effect of drugs that modify the
fatty acid metabolism on
urushiol-induced
contact dermatitis in mice.
Clofibrate, a peroxisomal proliferator in mice, increased the immune response to the urushiols from litre by 50%. Conversely, tetradecyl
glycidic acid, an inhibitor of the uptake of
fatty acids by mitochondria, decreased the
hypersensitivity to the
hapten. An increase in the level in
glutathione by treatment of the animals with 2-oxotiazolidin-4-carboxilic
acid lowered the response. Those findings strongly support a role for the
fatty acid oxidative metabolism in the processing and activation of urushiols in vivo.