PHORBOL 12-MYRISTATE 13-ACETATE CAN TRANSFORM MONOCYTE-DERIVED DENDRITIC CELLS TO DIFFERENT CELL-TYPES SIMILAR TO THOSE FOUND IN DERMATOFIBROMA - A POSSIBLE IN-VITRO MODEL OF THE HISTOGENESIS OF DERMATOFIBROMA

Dermatofibroma is composed largely of interlacing fascicles of slender spindle cells set within a loose collagenous stroma and of scattered foamy histiocytes and multinucleated giant cells. There is clear evide nce indicating that factor XIIIa+ dermal dendritic cells (DDCs) are th e cells constituting dermatofibromas. However, it is still unknown wha t stimulation is responsible for transforming DDCs into different cell types, producing different subtypes of dermatofibromas. Recently, it has become possible to obtain dendritic cells (DCs), that are identica l with DDCs in their phenotypic and functional characteristics, from t he culture of CD14(+) peripheral blood monocytes to which IL-4 and GM- CSF were added. Using these monocyte-derived DCs, we examined the abil ity of various cytokines, such as IL-1 beta, IL-3, IL-5, IL-6, IL-7, I L-8, ILIO, TNF alpha, TGF beta, M-CSF, IFN alpha, and IFN gamma, and p horbol 12-myristate 13-acetate (PMA), to induce different cell types o bserved in DFs. Among them, only PMA could induce a variety of cell ty pes such as histiocytic cells, fibroblastic spindle-shaped cells, and even multinucleated giant cells of Touton or foreign body type. Phenot ypically, all the induced cell types expressed CD1a, CD80, CD86, HLA-D R, and CD68 in a magnitude similar to that of non-treated monocyte-der ived DCs. The expression of factor XIIIa was strongest in histiocytic cells, moderate in fibroblastic cells, and weakest or negative in gian t cells. These data suggest that dermatofibromas are a kind of neoplas tic disease which is induced only by the effect of some tumor promoter on DDCs.