No Evidence for Histamine H4 Receptor in Human Monocytes

Abstract

The histamine H 4 receptor (H 4 R) is a classic pertussis toxinsensitive G i protein-coupled receptor that mediates increases in intracellular calcium concentration ([Ca 21 ] i ). The presence of H 4 R in human eosinophils has been rigorously documented by several independent groups. It has also been suggested that H 4 R is expressed in human monocytes, but this suggestion hinges in part on H 4 R antibodies with questionable specificity. This situation prompted us to reinvestigate H 4 R expression in human monocytes. As positive control, we studied human embryonic kidney 293T cells stably expressing the human H 4 R (hH 4 R). In these cells, histamine (HA) and the H 4 R agonistHowever, in quantitative real-time polymerase chain reaction studies we failed to detect hH 4 R mRNA in human monocytes and U937 promonocytes. In human monocytes, ATP and] i , but HA, UR-PI376, and 5-methylhistamine (a dual H 4 R/H 2 receptor agonist) did not. In U937 promonocytes and differentiated U937 cells, HA increased [Ca 21 ] i , but this increase was mediated via HA H 1 receptor. In conclusion, there is no evidence for the presence of H 4 R in human monocytes.

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…In mice, injection of an H 4 receptor agonist induced the migration of Langerhans cells in vivo (Gschwandtner et al, 2010). Chemotaxis of monocytes, gd T cells, and fibroblasts has also been shown to be mediated via the H 4 receptor (Damaj et al, 2007;Kohyama et al, 2010;Truta-Feles et al, 2010), although it was criticized (in particular for monocytes) that these data have only been published in single studies and have not been confirmed by other groups (Werner et al, 2014).…”

“…However, care must be taken in interpreting all of these data even where expression appears to correlate with pharmacological activity. For example, some groups report mRNA in monocytes and CD8 + T cells whereas others do not, which may be attributed to intrasubject variability in expression or in different cell isolation and detection methods used (Gantner et al, 2002;Ling et al, 2004;Dijkstra et al, 2007;Werner et al, 2014). In addition, although most of the pharmacological data are compelling, some details require further scrutiny.…”

Lack of Histamine H4-Receptor Expression Aggravates TNBS-Induced Acute Colitis Symptoms in Mice

“…Nevertheless, the regulation of the expression of the neutrophils attracting chemokines CXCL1, CXCL2, and of IL-6 and MPO connects H 4 R to the neutrophilic inflammatory reaction, and thereby to innate immune mechanisms. Cellular sources for CXCL1, CXCL2, and IL-6 are monocytes and macrophages, implying that these cells express a functional H 4 R. While functional expression of H 4 R in macrophages has already been demonstrated by us and others ( Cowden et al, 2013 ; Czerner et al, 2014 ), H 4 R expression on monocytes currently is controversially discussed ( Gschwandtner et al, 2013 ; Dib et al, 2014 ; Werner et al, 2014 ; Capelo et al, 2016 ). Nevertheless, at least in macrophages H 4 R function is described as pro-inflammatory, thus, probably cannot account for the anti-inflammatory effect in TNBS-induced colitis.…”

Histamine H4 Receptor in Allergic Dermatitis

“…On the other hand, HH4R antagonist (JNJ7777120) inhibits the production of CCL17 and CCL22 in the human monocyte-derived Langerhans cells of AD patients [33] . However, no evidence for the presence of HH4R in human monocyte is reported [34] . Further studies to HH4R on antigen presenting cells are needed.…”