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 H ₁, H ₂, and H ₃ histamine receptors. Histamine induced intracellular Ca ²⁺ 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 Ca ²⁺ transients, actin polymerization, and chemotaxis of immature DCs were due to stimulation of H ₁ and H ₃ subtypes. Modulation of IL-12 and IL-10 secretion by histamine involved the H ₂ and H ₃ 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.