Callesen Katrine T, Yuste-Montalvo Alma, Poulsen Lars K, Jensen Bettina M, Esteban Vanesa
Laboratory of Medical Allergology, Copenhagen University Hospital at Gentofte, DK-2900 Hellerup, Denmark.
Department of Allergy and Immunology, IIS-Fundación Jiménez Díaz, UAM, 28040 Madrid, Spain.
Biomedicines. 2021 Apr 19;9(4):439. doi: 10.3390/biomedicines9040439.
Human anaphylactic reactions largely involve an increase in vascular permeability, which is mainly controlled by endothelial cells (ECs). Due to the acute and serious nature of human anaphylaxis, in vivo studies of blood vessels must be replaced or supplemented with in vitro models. Therefore, we used a macromolecular tracer assay (MMTA) to investigate the EC permeability of three phenotypes of human ECs: artery (HAECs), vein (HSVECs) and microvessels from lung (HMLECs). ECs were stimulated with two fast-acting anaphylactic mediators (histamine and platelet-activating factor (PAF)) and one longer-lasting mediator (thrombin). At steady-state conditions, HSVEC monolayers were the most permeable and HMLEC the least (15.8% and 8.3% after 60 min, respectively). No response was found in ECs from artery or vein to any stimuli. ECs from microvessels reacted to stimulation with thrombin and also demonstrated a tendency of increased permeability for PAF. There was no reaction for histamine. This was not caused by missing receptor expression, as all three EC phenotypes expressed receptors for both PAF and histamine. The scarce response to fast-acting mediators illustrates that the MMTA is not suitable for investigating EC permeability to anaphylactic mediators.
人类过敏反应主要涉及血管通透性增加，这主要由内皮细胞（ECs）控制。由于人类过敏反应的急性和严重性，血管的体内研究必须用体外模型替代或补充。因此，我们使用大分子示踪剂测定法（MMTA）来研究三种人类ECs表型的EC通透性：动脉（HAECs）、静脉（HSVECs）和肺微血管（HMLECs）。用两种速效过敏介质（组胺和血小板活化因子（PAF））和一种长效介质（凝血酶）刺激ECs。在稳态条件下，HSVEC单层的通透性最高，HMLEC的通透性最低（60分钟后分别为15.8%和8.3%）。动脉或静脉的ECs对任何刺激均无反应。微血管的ECs对凝血酶刺激有反应，对PAF也表现出通透性增加的趋势。对组胺无反应。这不是由于缺乏受体表达，因为所有三种EC表型均表达PAF和组胺的受体。对速效介质的反应稀少表明MMTA不适合研究EC对过敏介质的通透性。
