Dendritic cells differently respond to haptens and irritants by their production of cytokines and expression of co‐stimulatory molecules

Abstract

After application of haptens to the skin, Langerhans cells (LC), i.e. immature dendritic cells (DC) in the skin, move to secondary lymphoid organs to sensitize naive T cells. During this process, LC become mature DC with augmented expression of various co-stimulatory molecules and MHC class II antigens. In this scenario, however, critical questions remain as to what kind of chemicals can induce this maturation process through what kind of mechanisms. To clarify these questions, we used monocyte-derived CD1a+ DC instead of LC since LC maturated spontaneously in vitro culture. After we confirmed that monocyte-derived DC showed at least phenotypic characteristics and a response to TNF-alpha similar to LC, we added various chemicals, i.e., dinitrochlorobenzene (DNCB), trinitrochlorobenzene (TNCB), NiCl2, ZnCl2, sodium dodecyl sulfate (SDS), or benzalkonium chloride (BC), to a culture of purified monocyte-derived CD1a+ DC. Of these chemicals, only NiCl2 and DNCB significantly increased the surface expression of CD54, CD86, HLA-DR antigen, and interleukin (IL)-1 beta production, while SDS, BC, or ZnCl2 could not augment them, except for weak augmentation of CD86 expression by SDS. The increase in the expression of CD86 induced by NiCl2 or DNCB was most remarkable, being observed in DC from almost all the subjects we examined. TNCB could also induce responses similar to those induced with DNCB, but the number of subjects whose DC responded to it was far less than that of subjects whose DC responded to NiCl2 or DNCB. In spite of the augmented CD86 expression on DC treated with DNCB or NiCl2, these chemicals induced different responses of DC in their expression of CD54 and HLA-DR and the production of IL-6 and tumor necrosis factor (TNF)-alpha. In addition, the up-regulation of CD86 expression on DC treated with DNCB was significantly suppressed by either anti-IL-1 beta or anti-TNF-alpha antibody, while that by NiCl2 was relatively insensitive to these antibody treatments. Finally, the protein kinase C inhibitor, H7, but not staurosporine, could suppress the augmentation of CD86 expression on DC induced either by NiCl2 or by DNCB. These data suggest that DC respond to some haptens by changing their expression of several co-stimulatory molecules and their production of cytokines with a resultant change in antigen-presenting function. They also suggest that these chemicals stimulate DC by different mechanisms. By these responses, DC may modulate the final immune response to chemicals.

Inhibitory effect of the polyinosinic‐polycytidylic acid/cationic liposome on the progression of murine B16F10 melanoma

“…CD14 + monocytes (2 Â 10 6 /mL) were cultured in complete medium containing 50 ng/mL recombinant human GM-CSF and 100 ng/mL recombinant human IL-4 for 5 days. One half of the culture medium was changed on days 3 and 5 [31,32]. On the 5th day, MoDC were treated with different concentrations of PIC liposome, empty liposome or 10 lg/mL LPS.…”

Effect of lipopolysaccharide, skin sensitizers and irritants on thioredoxin-1 expression in dendritic cells: relevance of different signalling pathways

“…During maturation, LC experiment morphological, functional and phenotypical changes, such as alteration of surface markers [2,20,58], production of cytokines and chemokines [3,16,20] and the induction of signal-transduction pathways [20,46]. Lipopolysaccharide (LPS) and skin sensitizers, in contrast to irritants, have been described to stimulate DC maturation [3,9,13,16,28,57,60,64]. However, the exact cellular and molecular mechanisms of DC activation are not yet fully understood, being this knowledge crucial to elucidate the mechanisms involved in the acquisition of skin sensitization.…”

Sulfamethoxazole and Its Metabolite Nitroso Sulfamethoxazole Stimulate Dendritic Cell Costimulatory Signaling

“…Indeed, studies with contact sensitizers have demonstrated that small protein-reactive compounds can induce dendritic cell maturation (30,32,33) at concentrations associated with significant cell death (34). It is interesting to note, therefore, that lymphocytes from hypersensitive patients are more susceptible to cell death in response to reactive drug metabolites than control cells (35)(36)(37)(38).…”