Histamine induced high mobility group box-1 release from vascular endothelial cells through H1 receptor.

Abstract

Background:

Systemic allergic reaction is characterized by vasodilation and vascular leakage, which causes a rapid, precipitous and sustained decrease in arterial blood pressure with a concomitant decrease of cardiac output. Histamine is a major mediator released by mast cells in allergic inflammation and response. It causes a cascade of inflammation and strongly increases vascular permeability within minutes through its four G-protein-coupled receptors (GPCRs) on endothelial cells. High mobility group box-1 (HMGB1), a nonhistone chromatin-binding nuclear protein, can be actively secreted into the extracellular space by endothelial cells. HMGB1 has been reported to exert pro-inflammatory effects on endothelial cells and to increase vascular endothelial permeability. However, the relationship between histamine and HMGB1-mediated signaling in vascular endothelial cells and the role of HMGB1 in anaphylactic-induced hypotension have never been studied.

Methods and results:

EA.hy 926 cells were treated with different concentrations of histamine for the indicated periods. The results showed that histamine induced HMGB1 translocation and release from the endothelial cells in a concentration- and time-dependent manner. These effects of histamine were concentration-dependently inhibited by d-chlorpheniramine, a specific H1 receptor antagonist, but not by H2 or H3/4 receptor antagonists. Moreover, an H1-specific agonist, 2-pyridylethylamine, mimicked the effects of histamine, whereas an H2-receptor agonist, 4-methylhistamine, did not. Adrenaline and noradrenaline, which are commonly used in the clinical treatment of anaphylactic shock, also inhibited the histamine-induced HMGB1 translocation in endothelial cells. We therefore established a rat model of allergic shock by i.v. injection of compound 48/80, a potent histamine-releasing agent. The plasma HMGB1 levels in compound 48/80-injected rats were higher than those in controls. Moreover, the treatment with anti-HMGB1 antibody successfully facilitated the recovery from compound 48/80-induced hypotension.

Conclusion:

Histamine induces HMGB1 release from vascular endothelial cells solely through H1 receptor stimulation. Anti-HMGB1 therapy may provide a novel treatment for life-threatening systemic anaphylaxis.

• Authors: Shangze Gao, Keyue Liu, Wenhan Ku, Dengli Wang, Hidenori Wake, Handong Qiao, Kiyoshi Teshigawara, Masahiro Nishibori
• Journal: Frontiers in immunology (Front Immunol) Vol. 13 Pg. 930683 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
• PMID: 36275732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Gao, Liu, Ku, Wang, Wake, Qiao, Teshigawara and Nishibori.

Chemical References

• Chlorpheniramine
• Chromatin
• Epinephrine
• Histamine
• Histamine H1 Antagonists
• Norepinephrine
• p-Methoxy-N-methylphenethylamine
• Receptors, G-Protein-Coupled
• Receptors, Histamine H1
• Hbp1 protein, rat

Topics

• Animals
• Rats
• Anaphylaxis (drug therapy)
• Chlorpheniramine (pharmacology)
• Chromatin
• Endothelial Cells
• Epinephrine
• Histamine
• Histamine H1 Antagonists (pharmacology, therapeutic use)
• Inflammation (drug therapy)
• Norepinephrine
• p-Methoxy-N-methylphenethylamine
• Receptors, G-Protein-Coupled
• Receptors, Histamine H1 (metabolism)