Stimulation of histamine H2- (and H1)-receptors activates Ca2+ influx in all-atrans-retinoic acid-differentiated HL-60 cells independently of phospholipase C or adenylyl cyclase

Abstract

In human neutrophils, histamine H2-receptors mediate activation of adenylyl cyclase (AC) and inhibition of N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced superoxide anion (O2-) formation, and in HL-60 promyelocytes, H2-receptors mediate parallel activation of AC, phospholipase C (PLC) and non-selective cation (NSC) channels. As all-trans-retinoic acid (RA) is successfully used in the differentiation therapy of acute promyelocytic leukaemia, we studied signal transduction in RA-differentiated HL-60 cells. Histamine and the H2-receptor agonist, impromidine, induced both rises in cAMP levels and cytosolic Ca2+ ([Ca2+]i). Substances acting at post-receptor sites to increase cAMP did not increase [Ca2+]i. H2- but not H1-receptor antagonists inhibited histamine-induced cAMP accumulation and rises in [Ca2+]i were more effectively inhibited by H2- than by H1-receptor antagonists. Histamine-induced rises in [Ca2+]i were completely dependent on the presence of extracellular Ca2+ and were abolished by the blocker of NSC channels, Gd3+, but were resistant to inhibition by pertussis toxin. Unlike FMLP, histamine did not activate PLC. The effects of FMLP on [Ca2+]i were less sensitive to blockade by Gd3+ than those of histamine, and there was no cross-desensitization between the two stimuli. FMLP, but not histamine, inhibited transiently thapsigargin-induced rises in [Ca2+]. Taken together, our results show that histamine activates AC-mediated cAMP accumulation in RA-differentiated HL-60 cells via H2-receptors and NSC channel-mediated Ca2+ influx via H2- (and H1)-receptors. Histamine-induced NSC channel activation is not the consequence of AC- or PLC stimulation and occurs, directly or indirectly, via pertussis toxin-insensitive guanine nucleotide-binding proteins. FMLP and histamine activate Ca2+ influx by different mechanisms. There are similarities in H2-receptor-mediated signal transduction between RA-differentiated HL-60 cells and HL-60 promyelocytes and differences between the former cells and neutrophils, indicating that RA-differentiated HL-60 cells must be considered as partially immature.

In U-937 promonocytes, misteltoe lectin I increases basal [Ca2+]i, enhances histamine H1- and complement C5a-receptor-mediated rises in [Ca2+]i, and induces cell death

“…Histamine-induced rises in [Ca 2+ ] i in HL-60 cells may be mediated via H 1 -or H 2 -receptors (Seifert et al 1992a(Seifert et al ,b, 1994Burde and Seifert 1996). In order to answer the question by which receptor subtype the histamine-induced rises in [Ca 2+ ] i in U-937 cells are mediated, we studied the effects of the highly potent H 1 -receptor antagonist, clemastine, and of the highly potent H 2 -receptor antagonist, famotidine.…”

“…Our finding that ATP-induced rises in U-937 cells were not enhanced by ML I (see Table 2) was not surprising because the ATP-induced rises in [Ca 2+ ] i remain virtually unaffected by differentiation of human myeloid cells (Dubyak et al 1988;WenzelSeifert and Seifert 1990). On first glance, it may appear unexpected that ML I did not induce responsiveness towards fMLP because this is a generally occurring phenomenon during myeloid differentiation (Seifert et al 1992a(Seifert et al , 1994Murphy 1994;Seifert and Burde 1996). Note, however, that fMLP is a bacteria-derived peptide and crucial for the effective killing of bacteria by phagocytes, whereas histamine and C5a are endogenous intercellular signal molecules and play a role also in numerous non-bacteriacaused inflammatory reactions.…”

“…An intriguing feature of apoptosis is its connection with differentiation processes. For example, all-trans-retinoic acid induces incomplete neutrophilic differentiation of HL-60 leukemia cells and apoptosis (Katagiri et al 1996;Burde and Seifert 1996). In U-937 promonocytes, interleukin 6 exhibits both differentiation-and apoptosis-inducing properties (Afford et al 1992).…”

“…Specifically, all-trans-retinoic acid is known to induce programmend cell death in HL-60 cells (Katagiri et al 1996), but there is no enhancement of H 1 -receptormediated rises in [Ca 2+ ] i in these cells compared to HL-60 promyelocytes (Seifert et al 1992b;Burde and Seifert 1996). In agreement with these data, we found that treatment of HL-60 cells with ML I induces cell death but no enhancement of H 1 -receptor-mediated rises in [Ca 2+ ] i .…”

Modulation of neutrophil oxidative burst via histamine receptors

“…The histamine H2 receptor couples to Gas proteins and induces AC-mediated cAMP accumulation. (Burde and Seifert, 1996;Reher et al, 2012) The signalling mechanisms for H4 receptors are much less well understood but it seems that their activation via Gai/Ga0 leads to inhibition of AC and an increase in intracellular Ca 2+ concentration (Stark, 2007;Marson, 2011).The recently identified histamine H4 receptor is primarily expressed on leukocytes and has been implicated in the activation of lymphocytes, eosinophils and mast cells in vitro. Although some studies and reviews have asserted that histamine H4 receptors are expressed on neutrophils or have described histamine H4 receptor-mediated effects on neutrophils (e.g.…”