title: Tumour necrosis factor-alpha induces Langerhans cell migration in humans.
abstract: The role of tumour necrosis factor (TNF)-alpha in the mobilization and migration of human epidermal Langerhans cells (LC) has been investigated. Intradermal injection of normal human volunteers with homologous recombinant TNF-alpha was found to cause a dose-dependent reduction in the frequency of LC within epidermal sheets 2 h later. Equivalent results were obtained when epidermal LC were identified on the basis of either CD1a or HLA-DR expression. At the dose of TNF-alpha used routinely (500 U), treatment resulted in an average reduction in LC density of approximately 24%. Treatment with TNF-alpha was associated with a perivascular polymorphonuclear infiltration at 2 h, but the epidermis appeared normal with neither fibrinoid necrosis nor vasculitis, and LC morphology was not affected significantly. These results demonstrate that TNF-alpha provides an important signal for LC migration in humans and is likely therefore to play a crucial part in the induction of cutaneous immune responses.
authors.affiliation: Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. Marie.Cumberbatch@CTL.ZENECA.com
authors.forename: M
authors.initials: M
authors.lastname: Cumberbatch
authors.forename: C E
authors.initials: CE
authors.lastname: Griffiths
authors.forename: S C
authors.initials: SC
authors.lastname: Tucker
authors.forename: R J
authors.initials: RJ
authors.lastname: Dearman
authors.forename: I
authors.initials: I
authors.lastname: Kimber
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000276:immunology; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007801:Langerhans Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018949:Antigens, CD1; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha