title: Transition metal sensing by Toll-like receptor-4: next to nickel, cobalt and palladium are potent human dendritic cell stimulators.
abstract: BACKGROUND
  Nickel was recently identified as a potent activator of dendritic cells through ligating with human Toll-like receptor (TLR)-4.
  
  
  OBJECTIVE
  Here, we studied an extended panel of transition metals neighbouring nickel in the periodic table of elements, for their capacity to activate human monocyte-derived dendritic cells (MoDCs).
  
  
  METHODS
  The panel included chromium, cobalt, and palladium, all of which are known to be frequent clinical sensitizers. MoDC activation was monitored by assessment of release of the pro-inflammatory mediator interleukin (IL)-8, a major downstream result of TLR ligation. Results The data obtained in the present study show that cobalt and palladium also have potent MoDC-activating capacities, whereas copper and zinc, but not iron and chromium, have low but distinct MoDC-activating potential. Involvement of endotoxin contamination in MoDC activation was excluded by Limulus assays and consistent stimulation in the presence of polymyxin B. The critical role of TLR4 in nickel-induced, cobalt-induced and palladium-induced activation was confirmed by essentially similar stimulatory patterns obtained in an HEK293 TLR4/MD2 transfectant cell line.
  
  
  CONCLUSIONS
  Given the adjuvant role of costimulatory danger signals, the development of contact allergies to the stimulatory metals may be facilitated by signals from direct TLR4 ligation, whereas other metal sensitizers, such as chromium, may rather depend on microbial or tissue-derived cofactors to induce clinical sensitization.
authors.affiliation: Department of Pathology, VU University Medical Centre, 1081 HV Amsterdam, The Netherlands.
authors.forename: Dessy
authors.initials: D
authors.lastname: Rachmawati
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.forename: Marleen I
authors.initials: MI
authors.lastname: Verstege
authors.forename: Joris
authors.initials: J
authors.lastname: Muris
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: Ingrid M W
authors.initials: IM
authors.lastname: van Hoogstraten
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002857:Chromium / Q000276:immunology / Q000378:metabolism; D003035:Cobalt / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D009532:Nickel / Q000276:immunology / Q000378:metabolism; D010165:Palladium / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism; D028561:Transition Elements / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016209:Interleukin-8; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D028561:Transition Elements; D002857:Chromium; D003035:Cobalt; D010165:Palladium; D009532:Nickel