Mechanisms in the induction of allergic contact dermatitis to nickel

Nickel is frequently reported as an agent causing allergic contact dermatitis in humans and was selected as an example for the investigation into the molecular mechanisms of the sensitivity. Nickel, as a hapten, may not constitute the complete antigen. The protein of cellular conjugates of nickel formed in the skin may represent the antigenic complexes, but the number and nature are unknown. In this submission, allergic contact dermatitis to nickel is reviewed; data on the immunological processes from various human and animal-model systems relevant to this problem are appraised and experimental investigations into the antigenic complexes of nickel are described. The albino guinea-pig was selected as a suitable animal model and a test system was developed to induce and elicit allergic contact dermatitis to nickel in this species. Under the exposure conditions of this system, an incidence of the sensitivity of 70-100% in a test population was experimentally induced. This consistently high incidence was not achieved by the use of standard published animal methods. Time-coursed In vivo exposure studies, employing 63NiCl2 as a radiotracer, were performed to qualitatively and quantatively examine the absorption and accumulation of nickel in the skin. The results indicated that soluble nickel salts are poorly absorbed across the skin. Maximum plasma levels were seen after 12 hours of exposure, although these represented only a very small percentage of the appled nickel salts (0.06%). Absorbed nickel was excreted in the urine. Microautoradiography of in vivo exposed skin indicated that transappendageal passage may be the main route of entry into the body. Accumulation of nickel was apparent in the highly keratinized areas of the skin, and labelling of basal and supra-basal epidermal cells was observed. Dermal accumulation was not seen. Fractionation of the in vivo exposed epidermis by zonal ultracentrification and gel filtration revealed four main areas of nickel localization. It was found associated with a microsomal fraction, with albumin, with an epidermal protein fraction (molecular weight 8,700) and with low molecular weight (