Abstract

The histamine H₄ receptor (H₄R) is a classic pertussis toxin-sensitive G_i protein–coupled receptor that mediates increases in intracellular calcium concentration ([Ca²⁺]_i). The presence of H₄R in human eosinophils has been rigorously documented by several independent groups. It has also been suggested that H₄R is expressed in human monocytes, but this suggestion hinges in part on H₄R antibodies with questionable specificity. This situation prompted us to reinvestigate H₄R expression in human monocytes. As positive control, we studied human embryonic kidney 293T cells stably expressing the human H₄R (hH₄R). In these cells, histamine (HA) and the H₄R agonist UR-PI376 (2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine) induced pertussis toxin–sensitive [Ca²⁺]_i increases. However, in quantitative real-time polymerase chain reaction studies we failed to detect hH₄R mRNA in human monocytes and U937 promonocytes. In human monocytes, ATP and N-formyl-l-methionyl-l-leucyl-l-phenylalanine increased [Ca²⁺]_i, but HA, UR-PI376, and 5-methylhistamine (a dual H₄R/H₂ receptor agonist) did not. In U937 promonocytes and differentiated U937 cells, HA increased [Ca²⁺]_i, but this increase was mediated via HA H₁ receptor. In conclusion, there is no evidence for the presence of H₄R in human monocytes.