MUTZ-3-derived dendritic cells as an in vitro alternative model to CD34+ progenitor-derived dendritic cells for testing of chemical sensitizers

The cytokine-dependent CD34+ human acute myeloid leukaemia cell line MUTZ-3 was used to generate immature dendritic-like cells (MUTZ-3 DC) and their validity as an alternative to primary CD34+ progenitor-derived DC (CD34–DC) for testing chemical-induced sensitization was assessed. Expression levels of the DC maturation markers HLA-DR, CD86, CD83 and CD11c were studied using flow cytometry after 24 and 48 h exposure to the model compound nickel sulphate (100 and 300 μM). No maturation of MUTZ-3 DC was observed, whereas significantly upregulated expression levels of CD83 and CD86 were noticed in CD34–DC after 24 h treatment with 300 μM nickel sulphate compared to control cells.Differential expression of the cytokine genes IL1β, IL6, IL8, CCL2, CCL3, CCL3L1, CCL4 was analyzed using real-time RT-PCR after 6, 10 and 24 h of nickel sulphate exposure. In response to 100 μM nickel sulphate MUTZ-3 DC revealed slightly upregulated mRNA levels after 24 h, whereas 300 μM induced transcription of CCL3, CCL3L1 and IL8 significantly after 6 or 10 h. These cytokine data correspond to the previously observed effects of 100 μM nickel sulphate in CD34–DC.Our findings underline the stimulatory capacity of nickel sulphate in MUTZ-3 DC with regard to cytokine mRNA induction, but not surface marker expression. Compared to CD34–DC, however, the studied endpoint markers seemed to be less inducible, making the MUTZ-3 DC model in its presented form less suitable for in vitro testing of sensitization. Further assessment of MUTZ-3 DC using other differentiation protocols and an extended set of chemicals will be required to reveal whether this cell line may be a valid alternative model system to primary CD34–DC.