Expression and function of histamine receptors in human monocyte-derived dendritic cells.

BACKGROUND Histamine is a well-known mediator eliciting different responses in immune and nonimmune cells, but its role in modulating dendritic cell (DC) functions has been marginally investigated. OBJECTIVE The purpose of this investigation was to analyze whether human monocyte-derived DCs express functional histamine receptors according to their maturation stage. METHODS DCs were derived from monocytes and used as immature or LPS-differentiated cells. DCs were tested for histamine receptor expression, chemotaxis, cytokine release, and the capacity to induce T-cell differentiation in response to specific histamine receptor agonists. RESULTS Immature and mature DCs expressed the mRNA for H1, H2, and H3 histamine receptors. Histamine induced intracellular Ca2+ transients, actin polymerization, and chemotaxis in immature DCs. Maturation of DCs resulted in the loss of these responses. In maturing DCs, however, histamine dose-dependently enhanced intracellular cAMP levels and stimulated IL-10 secretion while inhibiting production of IL-12. As a consequence, histamine might contribute to the impairment of generation of allogeneic type 1 responses via maturing DCs. Specific histamine receptor agonists or antagonists revealed that Ca2+ transients, actin polymerization, and chemotaxis of immature DCs were due to stimulation of H1 and H3 subtypes. Modulation of IL-12 and IL-10 secretion by histamine involved the H2 and H3 receptors exclusively. CONCLUSIONS Our study suggests that histamine has important biological effects on DC activities, opening the possibility that histamine released during inflammatory or immune responses could regulate DC functions and ultimately favor type 2 lymphocyte-dominated immunity.