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.
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.
EA。将hy926细胞用不同浓度的组胺处理指定的时期。结果表明,组胺以浓度和时间依赖性方式诱导HMGB1易位和从内皮细胞释放。组胺的这些作用被d-氯苯那敏浓度依赖性地抑制,一种特定的H1受体拮抗剂,但不是H2或H3/4受体拮抗剂。此外,H1特异性激动剂,2-吡啶基乙胺,模仿组胺的作用,而H2受体激动剂,4-甲基组胺,没有。肾上腺素和去甲肾上腺素,这是临床上常用的过敏性休克的治疗方法,还抑制了组胺诱导的HMGB1在内皮细胞中的易位。因此,我们通过静脉内注射化合物48/80(一种有效的组胺释放剂)建立了过敏性休克的大鼠模型。注射化合物48/80的大鼠的血浆HMGB1水平高于对照组。此外,抗HMGB1抗体治疗成功促进了化合物48/80诱导的低血压的恢复.
组胺仅通过H1受体刺激诱导血管内皮细胞释放HMGB1。抗HMGB1治疗可能为危及生命的全身性过敏反应提供新的治疗方法。