title: Formation of antigenic quinolone photoadducts on Langerhans cells initiates photoallergy to systemically administered quinolone in mice.
abstract: Quinolone antibacterial agents are well known to cause photoallergy as a side-effect. Murine photoallergy to fluoroquinolones is a T cell-mediated immune response, evoked either by systemic fluoroquinolone and subsequent exposure of skin to ultraviolet A light or by subcutaneous injection of fluoroquinolone-photomodified epidermal cells. In this photosensitivity, epidermal Langerhans cells may be photomodified initially with the drug and thus present photohaptenic moieties to sensitize and restimulate T cells. Although we have shown that Langerhans cells photocoupled in vitro with fluoroquinolones are capable of stimulating sensitized T cells, it remains unclear whether systemically given fluoroquinolone photomodifies Langerhans cells upon ultraviolet A irradiation of the skin and the Langerhans cells become photohapten-bearing, T cell-stimulatory cells. In a murine model of fleroxacin photoallergy induced by intraperitoneal injection of the drugs plus ultraviolet A irradiation of skin, we found that Langerhans cells as well as keratinocytes are photoderivatized with fleroxacin as demonstrated with a fluoroquinolone-specific monoclonal antibody. Langerhans-cell-enriched epidermal cells prepared from mice treated with fleroxacin and ultraviolet A induced proliferation of sensitized T cells, indicating that photomodified Langerhans 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 capacity of Langerhans cells presumably because of drug phototoxicity. Our study suggests that Langerhans cells serve as photoantigen-presenting cells in drug photoallergy.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. a41114@hama-med.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Ohshima
authors.forename: N
authors.initials: N
authors.lastname: Seo
authors.forename: M
authors.initials: M
authors.lastname: Takigawa
authors.forename: Y
authors.initials: Y
authors.lastname: Tokura
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000032:analysis*; D000941:Antigens / Q000096:biosynthesis; D017454:Dermatitis, Photoallergic / Q000209:etiology*; D016576:Fleroxacin / Q000008:administration & dosage / Q000032:analysis; D007274:Injections, Intraperitoneal; D015603:Keratinocytes / Q000737:chemistry; D007801:Langerhans Cells / Q000737:chemistry* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015363:Quinolones / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D000890:Anti-Infective Agents; D000941:Antigens; D015363:Quinolones; D016576:Fleroxacin