The purpose of this project is to construct in vitro models of epidermal cell cytotoxicity as mechanisms of skin disease. Although antibody dependent cellular cytotoxicity (ADCC) is the mechanism to be most actively studied, we will also examine complement mediated lysis, natural killing, and eventually classical cell mediated cytotoxicity of epidermal targets. These in vitro models will be used to study our hypothesis that ADCC of epidermal cells is an important mechanism of cutaneous lupus erythematosus, using ultraviolet light transformed cells or epidermal cells specifically coated with nucleoprotein antigens. Similar experiments will be performed using herpes simplex antigen coated epidermal cells and endothelial cells to construct an in vivo model of post-herpetic erythema multiforme. Models of ADCC in pemphigus vulgaris, bullous pemphigoid, lichen planus, and maculopapular drug eruptions will also be constructed.

National Institute of Health (NIH)
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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University of Colorado Denver
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Furukawa, F; Lyon, M B; Norris, D A (1989) Susceptible cytotoxicity to ultraviolet B light in fibroblasts and keratinocytes cultured from autoimmune-prone MRL/Mp-lpr/lpr mice. Clin Immunol Immunopathol 52:460-72
Lee, L A; Norris, D A (1989) Mechanisms of cutaneous tissue damage in lupus erythematosus. Immunol Ser 46:359-86
Brice, S L; Norris, D A; Weston, W L et al. (1988) Development of an in vitro keratinocyte model for use in the study of HSV specific cytotoxicity. J Invest Dermatol 90:629-33
Furukawa, F; Huff, J C; Lyons, M B et al. (1988) Characterization and practical benefits of keratinocytes cultured in strontium-containing serum-free medium. J Invest Dermatol 90:690-6
Norris, D A; Kissinger, R M; Naughton, G M et al. (1988) Evidence for immunologic mechanisms in human vitiligo: patients' sera induce damage to human melanocytes in vitro by complement-mediated damage and antibody-dependent cellular cytotoxicity. J Invest Dermatol 90:783-9
Norris, D A; Osborn, R; Robinson, W et al. (1987) Isotretinoin produces significant inhibition of monocyte and neutrophil chemotaxis in vivo in patients with cystic acne. J Invest Dermatol 89:38-43
Furukawa, F; Huff, J C; Weston, W L et al. (1987) Serum-free serial culture of adult human keratinocytes from suction-blister roof epidermis. J Invest Dermatol 89:460-3
Wikner, N E; Huff, J C; Norris, D A et al. (1986) Study of HLA-DR synthesis in cultured human keratinocytes. J Invest Dermatol 87:559-64
Lee, L A; Weston, W L; Krueger, G G et al. (1986) An animal model of antibody binding in cutaneous lupus. Arthritis Rheum 29:782-8
Lee, L A; Norris, D A; Weston, W L (1986) Neonatal lupus and the pathogenesis of cutaneous lupus. Pediatr Dermatol 3:491-7

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