Langerhans cell migration patterns from sheep skin following topical application of carcinogens

Application of tumour promoters or complete chemical carcinogens to skin alters the density and/or morphology of epidermal Langerhans cells (LC). To examine the hypothesis that these chemical carcinogens alter LC migration kinetics from the epidermis, pseudoafferent lymphatic vessels draining defined areas of carcinogen treated sheep skin were cannulated and the number of LC migrating enumerated using indirect immunofluorescence and flow cytometry. The complete carcinogen benzo[a]pyrene (BP) and the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) caused an immediate two to four-fold increase in the rate of LC migration, while the tumour initiator urethane did not alter LC migration. The antigenicity of the carcinogens utilized was assessed in contact hypersensitivity experiments in mice. BP and TPA were mildly antigenic whereas urethane failed to initiate a contact hypersensitivity response in sensitized mice. It is concluded that the initial increase in LC migration from skin following the application of the tumour promoter TPA and the complete carcinogen BP is partly due to LC recognizing these carcinogens as antigens.