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:
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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)
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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
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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)
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