| dc.description.abstract | Background. Nickel was recently identified as a potent activator of dendritic cells
through ligating with human Toll-like receptor (TLR)-4.
Contact Dermatitis
Objectives. Here, we studied an extended panel of transition metals neighbouring
nickel in the periodic table of elements, for their capacity to activate human monocytederived
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 theadjuvant role of costimulatory danger signals, thedevelopment
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. | en_US |
