Glycolysis is integral to histamine-induced endothelial hyperpermeability.
Glycolysis is integral to histamine-induced endothelial hyperpermeability.
复制标题
糖酵解是组胺诱导的内皮细胞通透性增高的组成部分。
DOI：
10.1096/fj.202001634r
复制
发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Sprott D
中科院分区：
文献类型：
--
作者：
Ziogas A;Sajib MS;Lim JH;Alves TC;Das A;Witt A;Hagag E;Androulaki N;Grossklaus S;Gerlach M;Noll T;Grinenko T;Mirtschink P;Hajishengallis G;Chavakis T;Mikelis CM;Sprott D
组胺诱导的血管渗漏是过敏性病理学（包括速发过敏反应）的核心过程。在这里，我们表明，糖酵解是不可或缺的组胺诱导的内皮屏障破坏和通透性增高。组胺通过组胺受体1和磷脂酶C β信号通路快速增强内皮细胞糖酵解。一致地，用3-（3-吡啶基）-1-（4-吡啶基）-2-丙烯-1-酮（3 PO）部分抑制糖酵解通过消除组胺诱导的肌动球蛋白收缩、粘着斑连接形成和内皮屏障破坏来防止组胺诱导的人微血管内皮细胞的高通透性。药理学阻断糖酵解与3 PO在小鼠中减少组胺诱导的血管通透性过高，防止血管渗漏的被动皮肤过敏反应和保护全身过敏反应。总之，我们阐明了糖酵解在组胺诱导的内皮屏障完整性破坏中的作用。因此，我们的数据指出，内皮糖酵解作为一种新的治疗目标，人类病理学相关的过度血管渗漏，如全身过敏反应。
Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling. Consistently, partial inhibition of glycolysis with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) prevented histamine-induced hyperpermeability in human microvascular endothelial cells, by abolishing the histamine-induced actomyosin contraction, focal adherens junction formation and endothelial barrier disruption. Pharmacologic blockade of glycolysis with 3PO in mice reduced histamine-induced vascular hyperpermeability, prevented vascular leakage in passive cutaneous anaphylaxis and protected from systemic anaphylaxis. In conclusion, we elucidated the role of glycolysis in histamine-induced disruption of endothelial barrier integrity. Our data thereby point to endothelial glycolysis as a novel therapeutic target for human pathologies related to excessive vascular leakage, such as systemic anaphylaxis.