Mouse model for protoporphyria. II. Cellular and subcellular events in the photosensitivity flare of the skin.

Acute phototoxic reactions were induced by long-wave ultraviolet light (UV-A) in mice with griseofulvin-induced protoporphyria. The clinical response was characterized by erythema, pronounced edema, and purpura. Tracer experiments and electron microscopy revealed pronounced vascular damage and leakage of vascular contents, whereas the epidermis and all other dermal components were intact. There was selective destruction of endothelial cells and damage of the basal lamina of the vessels. This striking vascular injury was absent from nonprotoporphyric UV-A-irradiated mice and from protoporphyric and nonprotoporphyric mice exposed to short-wave ultraviolet light (UV-B). Patients with erythropoietic protoporphyria (EPP) exhibit an identical, selective damage of blood vessels when irradiated with UV-A or sunlight but not with UV-B alone. It is hypothesized that in both murine protoporphyria and EPP, endothelial cells are photosensitized by protoporphyrin circulating in the serum and that photosensitized endothelia represent the primary cellular target of the photochemical reaction induced by UV-A.