title: Photohardening restores the impaired neutrophil responsiveness to chemoattractants leukotriene B4 and formyl-methionyl-leucyl-phenylalanin in patients with polymorphic light eruption.
abstract: A failure to induce immune suppression after UV exposure has been implicated in the pathogenesis of polymorphic light eruption (PLE). This immunological resistance has been linked to an impaired neutrophil infiltration into the skin following UV exposure. Therapeutic photohardening can restore this abnormal neutrophil infiltration in PLE skin and is thought to be responsible for the prophylactic efficacy. The aim of this study was to elucidate the pathogenic mechanism of the described neutrophil deficiency in PLE. Peripheral blood neutrophil responses to the chemoattractants leukotriene B4 (LTB(4)) and formyl-methionyl-leucyl-phenylalanin (fMLP) were investigated in vitro. Samples from 10 patients with PLE before and after 6 weeks of photohardening therapy were assessed. Flow cytometry was used to measure the changes associated with neutrophil activation. We found a significantly reduced neutrophil responsiveness to LTB(4) and fMLP in PLE patients, which was restored to normal levels after phototherapy. Indeed, PLE neutrophil responsiveness to these two chemoattractants after (but not before) phototherapy was similar to that of age- and sex-matched healthy control subjects. This indicates that an abnormal chemotactic potential to neutrophils is a crucial factor in the pathogenesis of PLE. Normalization following photohardening may therefore account for the therapeutic efficacy by restoring UV-induced neutrophil skin infiltration. Our results reveal a completely novel pathogenic mechanism involved in PLE and offer unique targets for therapy.
authors.affiliation: Research Unit for Photodermatology, Department of Dermatology, Medical University of Graz, Graz, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gruber-Wackernagel
authors.forename: Akos
authors.initials: A
authors.lastname: Heinemann
authors.forename: Viktoria
authors.initials: V
authors.lastname: Konya
authors.forename: Scott N
authors.initials: SN
authors.lastname: Byrne
authors.forename: Tej Pratap
authors.initials: TP
authors.lastname: Singh
authors.forename: Angelika
authors.initials: A
authors.lastname: Hofer
authors.forename: Franz
authors.initials: F
authors.lastname: Legat
authors.forename: Peter
authors.initials: P
authors.lastname: Wolf
mesh_terms: D000328:Adult; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology*; D008027:Light; D008297:Male; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D018375:Neutrophil Activation / Q000187:drug effects / Q000528:radiation effects; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000528:radiation effects; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D010787:Photosensitivity Disorders / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010789:Phototherapy; D014466:Ultraviolet Rays
chemical_list: D002630:Chemotactic Factors; D007975:Leukotriene B4; D009240:N-Formylmethionine Leucyl-Phenylalanine