Heidarzadeh-Asl Sima, Maurer Marcus, Kiani Amir, Atiakshin Dmitrii, Stahl Skov Per, Elieh-Ali-Komi Daniel
Regenerative Medicine Research Center (RMRC), Kermanshah University of Medical Sciences, Kermanshah, Iran.
Institute of Allergology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Immunology and Allergology, Berlin, Germany.
J Allergy Clin Immunol. 2025 Apr;155(4):1095-1114. doi: 10.1016/j.jaci.2024.12.1081. Epub 2024 Dec 27.
Histamine (CHN, molecular weight 111.15 g/mol) is a well-studied endogenous biogenic amine composed of an imidazole ring attached to an ethylamine side chain. It has a limited half-life of a few minutes within tissues and in circulation. Several cell types including mast cells (MCs), basophils, platelets, histaminergic neurons, and enterochromaffin cells produce varying amounts of histamine using histidine decarboxylase. However, only MCs and basophils have complex mechanisms to pack and store histamine in granules along with other mediators using serglycin and its carried glycosaminoglycan side chains. Relatively low granule pH (∼5.5) supports the binding of stored histamine to heparin, whereas exposure to neutral pH after degranulation weakens the binding and histamine becomes liberated. Histamine exerts multifaceted regulatory biofunctions by engaging its 4 types of heptahelical G protein-coupled receptors (H1R-H4R), which have different expression profiles and functions. MCs express H1R, H2R, and H4R, which gives them a dual role in histamine biology as producers and responsive target cells. Histamine plays a role in a variety of physiologic and pathologic processes such as cell proliferation, differentiation, hematopoiesis, vascular permeability, embryogenesis, tissue regeneration, and wound healing. The emergence of histamine receptor-deficient mouse models and the development of multiple histamine receptor agonists and antagonists have helped researchers better understand these physiologic and pathogenic functions of histamine. We review the biology of histamine with a focus on immunologic aspects and the role of histamine in allergy and MC biology.
组胺（C₅H₉N₃，分子量111.15 g/mol）是一种经过充分研究的内源性生物胺，由连接在乙胺侧链上的咪唑环组成。它在组织和循环中的半衰期较短，只有几分钟。包括肥大细胞（MC）、嗜碱性粒细胞、血小板、组胺能神经元和肠嗜铬细胞在内的几种细胞类型，利用组氨酸脱羧酶产生不同数量的组胺。然而，只有MC和嗜碱性粒细胞具有复杂的机制，可利用丝甘氨酸及其携带的糖胺聚糖侧链将组胺与其他介质一起包装并储存在颗粒中。相对较低的颗粒pH值（约5.5）有助于储存的组胺与肝素结合，而脱颗粒后暴露于中性pH值会削弱这种结合，组胺从而释放出来。组胺通过与4种七螺旋G蛋白偶联受体（H1R - H4R）结合发挥多方面的调节生物功能，这些受体具有不同的表达谱和功能。MC表达H1R、H2R和H4R，这使其在组胺生物学中作为产生者和反应性靶细胞发挥双重作用。组胺在多种生理和病理过程中发挥作用，如细胞增殖、分化、造血、血管通透性、胚胎发生、组织再生和伤口愈合。组胺受体缺陷小鼠模型的出现以及多种组胺受体激动剂和拮抗剂的开发，帮助研究人员更好地理解了组胺的这些生理和致病功能。我们综述组胺的生物学，重点关注免疫学方面以及组胺在过敏和MC生物学中的作用。
