As the induction of contact hypersensitivity is the result of a series of cellular processes, including maturation and migration of epidermal dendritic cells (Langerhans cells (LC)), a battery of assays based on these in vivo events might provide a robust in vitro predictability model for distinguishing sensitizers from non-sensitizers. Therefore, assays with read-out for changes in CD86 expression and CXCL8 secretion were compared with a novel functional assay based on the in vitro migratory behaviour of LC. In all three assays LC derived from the human myeloid-leukaemia-cell-line MUTZ-3 (MUTZ-LC) were used. Exposure of MUTZ-LC to a panel of five sensitizers and three non-sensitizers resulted in increased CD86 expression in only 3/5 sensitizers, but also in 1/3 non-sensitizers. In contrast, CXCL8 secretion was uniformly increased after exposure to all sensitizers, but not after exposure to non-sensitizers. In a transwell migration assay, preferential migration of sensitizer-exposed MUTZ-LC towards CXCL12 was observed (5/5 sensitizers), whereas non-sensitizer-exposed MUTZ-LC only migrated towards CCL5 (3/3 non-sensitizers). In conclusion, the novel MUTZ-LC migration assay and analysis of CXCL8 secretion proved to be more successful than analysis of CD86 in predicting sensitizers from non-sensitizers and therefore warrant further investigation in the field of in vitro assay development.
Published by Elsevier Ltd.