Stimulation of Histamine Receptors of Human Monocytoid and Hepatoma‐Derived Cell Lines and Mouse Hepatocytes Modulates the Production of the Complement Components C3, C4, Factor B, and C2

Abstract

The influence of histamine (and the related agonists and antagonists) alone or in the presence of recombinant human interleukin 1 alpha (IL-1 alpha) and gamma interferon (IFN-gamma) was studied on the production of complement components C3, C2, factor B, and C4 in vitro with human monocytoid cell line U937, hepatoma-derived cell line HepG2, and mouse hepatocytes. Both U937 and HepG2 cells responded to histamine through H1 and H2 histamine receptors. The effect of histamine on the biosynthesis and gene expression of complement proteins was predominantly enhancing via the H1 histamine receptors and inhibitory through the H2 receptors. The actual predominance of the histamine receptor involved (and the outcome of the ligand interaction) seemed to be greatly affected by the simultaneous activation of the cells by IL-1 or IFN-gamma.

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

“…Specifically, U-937 cells contain histamine (Gespach et al 1986) and can produce complement components (Falus et al 1989). Intriguingly, stimulation of H 1 -receptors enhances complement factor production in U-937 cells (Falus et al 1989). Even more intriguingly, the presence of H 1 -and C5a receptors per se, i.e.…”

Histamine Modulates the Interleukin‐6‐Regulated Acute Phase Protein Synthesis in Cultured Murine Hepatocytes

“…Exposure of murine hepatocytes to histamine alone, for periods of up to 48 h, only slightly affected the production of fibrinogen and C3, while in murine peritoneal macrophages histamine enhanced the consitutive complement synthesis [8]. We described earlier [12] a HI histamine receptor-dependent enhancement of constitutive C3 production in HepG2. The effect of histamine on the biosynthesis and gene expression of complement proteins was predominantly stimulatory through receptors HI and inhibitory through H2 receptors in human monocytoid eell line U937 and human hepatoma HepG2 cells [12.…”

“…The molecular details of the selective potentiating effect of histamine on the activity of IL-6 remain unelucidated. However, one can assume a possible regulation via the expression of IL-6 receptor on murine hepatocytes, since the histamine seems not to act alone on mouse hepatocytes and a definite effect of histamine on the expression of IL-6 receptor on different monocytoid, B lymphoid and hepatoma cell lines has recently been described [12]. Actually, histamine decreased the number of '"I-IL-6 binding sites on human hepatomas [14].…”

“…As an alternative explanation, the interaction between IL-6 and histamine may also be regulated further down-stream, at the level of signal transduction. This alternative has been proposed since when C3 synthesis by murine hepatocytes was examined, a complete elimination of the strong stimulatory effect of recombinant interferon-"/ by histamine was found [12]. Further functional and molecular studies on the effect of histamine on the IL-6 expression, as well as lL-6 receptor expression and hepatic IL-6 signal transduction, should elucidate this interaction.…”

Differences in the Complement Activation Induced by Preformed and Nascent Immune Complexes

“…30 min at 3,000 rpm/min. The C3, C4 and Bf content of the PEG precipitates was then measured by ELISA methods [9], Clr-Cls-Cl INH (Classical Pathway) ELISA. C1 rCls-Cl INH complexes were measured by the method of Nilsson and Bäck [10], C3b(Bb)P (Alternative Pathway) ELISA.…”