Tumour necrosis factor-alpha induces Langerhans cell migration in humans.
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.
Cumberbatch
M
M
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire SK10 4TJ, UK. Marie.Cumberbatch@CTL.ZENECA.com
Griffiths
C E
CE
Tucker
S C
SC
Dearman
R J
RJ
Kimber
I
I
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*
D018949:Antigens, CD1; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha