Differentiation of monocytes into macrophages induces the upregulation of histamine H1 receptor

BackgroundHistamine modulates several functions in human monocytes, macrophages, and dendritic cells. However, responses elicited by histamine differ depending on cell type, suggesting variable expression of histamine receptors in the monocyte/macrophage lineage.ObjectiveWe sought to examine whether the expression of H1 receptors was regulated by cell differentiation of human monocytes into macrophages or dendritic cells.MethodsExpression of H1 receptor was evaluated by RT-PCR and western blot in monocytes, monocyte-derived macrophages (MDMs), monocyte-derived dendritic cells (DCs) and human lung macrophages (HLMs).ResultsExpression of H1 receptor mRNA and protein was higher in HLMs and DCs than in monocytes. H1 expression was approximately 15-fold and 4-fold higher in MDMs and HLMs, respectively, as compared with that seen in monocytes. H1 receptor protein was undetectable in monocytes, whereas it was conspicuous in MDMs. Simultaneous analysis of H2 and H1 mRNA expression indicated that the H2/H1 ratio decreased from 202.7 ± 14.8 in monocytes to 2.2 ± 0.4 in MDM and 39.5 ± 5.0 in DCs. Incubation of monocytes with histamine neither affected intracellular Ca2+ concentrations nor influenced IL-8 production. In contrast, histamine rapidly induced a Ca2+ signal and stimulated IL-8 production in MDMs. Both effects were inhibited by H1 blockade with levocetirizine, but not by H2 blockade with ranitidine.ConclusionsDifferentiation of monocytes into macrophages or dendritic cells is associated with profound changes of histamine receptor expression. Upregulation of H1 receptors confers on macrophages the capacity of being activated by histamine.Clinical implicationsRegulation of H1 and H2 receptor expression in the monocyte/macrophage lineage can be relevant to the pathogenesis of allergic inflammation.