Formation of antigenic quinolone photoadducts on langerhans cells initiates photoallergy to systemically administered quinolone in mice

Quinolone antibacterial agents are well known to cause photoallergy as a si de-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated imm une response, evoked either by systemic fluoroquinolone and subsequent expo sure of skin to ultraviolet A light or by subcutaneous injection of fluoroq uinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus pre sent photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinol ones are capable of stimulating sensitized T cells, it remains unclear whet her systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photo hapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin p hotoallergy induced by intraperitoneal injection of the drugs plus ultravio let A irradiation of skin, we found that Langerhans cells as well as kerati nocytes are photoderivatized with fleroxacin as demonstrated with a fluoroq uinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal c ells prepared from mice treated with fleroxacin and ultraviolet A induced p roliferation of sensitized T cells, indicating that photomodified Langerhan s cells are functional. There was an optimal range of ultraviolet A dose to quantitatively and qualitatively form fleroxacin-photomodified Langerhans cells, as excess ultraviolet A rather reduced the photoantigen-presenting c apacity of Langerhans cells presumably because of drug phototoxicity. Our s tudy suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy.