Inhibition of contact sensitizer-induced migration of human Langerhans cells by matrix metalloproteinase inhibitors

Emigration of Langerhans cells (LC) from the epidermis upon exposure to con tact sensitizers is regarded as an essential event in the development of co ntact sensitization, Since migration of several types of cells depends on t he activity of matrix metalloproteinases (MMPs), in the present study we te sted whether MMP inhibitors (BB94, BB2116 and CT1166) can prevent the emigr ation of LC in cultured skin explants, which were exposed to a contact sens itizer (NiSO4). Epicutaneous application of NiSO4 significantly reduced the number of LC within the epidermis and the remaining LC were localized alon g the epidermal-dermal junction indicating the emigration of LC, In the pre sence of each of the MMP inhibitors tested, NiSO4-induced migration of LC w as strongly decreased, Since after the epicutaneous application of contact sensitizer, its presentation by skin LC is essential for the development of contact sensitization instead of the development of antigen-specific toler ance, our results suggest that the use of MMP inhibitors may be beneficial for the prevention of contact sensitization of the host.