Histamine induces the generation of monocyte-derived dendritic cells that express CD14 but not CD1a.

The local cytokine environment and the presence of stimulatory signals determine whether monocytes acquire dendritic cell or macrophage characteristics and functions. In this study, we examined the effect of histamine, a prototypic mediator of allergic inflammation, on the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4-driven differentiation of monocytes into monocyte-derived dendritic cells (MoDC), which typically showed CD1a+CD14- phenotype. Monocytes from healthy adult donors were cultured with GM-CSF and IL-4 in the presence or absence of histamine, and the phenotypes and function of these cells were analyzed. Histamine induced the generation of CD1a-CD14+ cells, which exhibited cytological and phenotypical characteristics of dendritic cells (DC), showed enhanced phagocytic activity and cytokine-producing capacity, but demonstrated weak allo-stimulatory capacity compared with CD1a+CD14- MoDC. The inhibitory effects of histamine on CD1a+CD14- MoDC differentiation were antagonized by cimetidine, an H2 receptor antagonist, but not by H1 and H3 receptor blockers, and were mimicked by an H2 receptor agonist. Culture supernatant of histamine-treated monocytes also inhibited CD1a+CD14- MoDC differentiation, which was restored by the removal of IL-10. These results suggest that histamine-driven CD1a-CD14+ DC amplify their antigen-independent inflammatory reaction and may contribute to the exacerbation of allergic diseases.