Piotin Anays, Oulehri Walid, Charles Anne-Laure, Tacquard Charles, Collange Olivier, Mertes Paul-Michel, Geny Bernard
Physiology and Functional Exploration Service, Strasbourg University Hospital, 67000 Strasbourg, France.
Division of Asthma and Allergy, Chest Diseases Department, Strasbourg University Hospital, 67000 Strasbourg, France.
Antioxidants (Basel). 2024 Jul 29;13(8):920. doi: 10.3390/antiox13080920.
Anaphylaxis, an allergic reaction caused by the massive release of active mediators, can lead to anaphylactic shock (AS), the most severe and potentially life-threatening form of anaphylactic reaction. Nevertheless, understanding of its pathophysiology to support new therapies still needs to be improved. We performed a systematic review, assessing the role and the complex cellular interplay of mitochondria and oxidative stress during anaphylaxis, mast cell metabolism and degranulation. After presenting the main characteristics of anaphylaxis, the oxidant/antioxidant balance and mitochondrial functions, we focused this review on the involvement of mitochondria and oxidative stress in anaphylaxis. Then, we discussed the role of oxidative stress and mitochondria following mast cell stimulation by allergens, leading to degranulation, in order to further elucidate mechanistic pathways. Finally, we considered potential therapeutic interventions implementing these findings for the treatment of anaphylaxis. Experimental studies evaluated mainly cardiomyocyte metabolism during AS. Cardiac dysfunction was associated with left ventricle mitochondrial impairment and lipid peroxidation. Studies evaluating in vitro mast cell degranulation, following Immunoglobulin E (IgE) or non-IgE stimulation, revealed that mitochondrial respiratory complex integrity and membrane potential are crucial for mast cell degranulation. Antigen stimulation raises reactive oxygen species (ROS) production from nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and mitochondria, leading to mast cell degranulation. Moreover, mast cell activation involved mitochondrial morphological changes and mitochondrial translocation to the cell surface near exocytosis sites. Interestingly, antioxidant administration reduced degranulation by lowering ROS levels. Altogether, these results highlight the crucial role of oxidative stress and mitochondria during anaphylaxis and mast cell degranulation. New therapeutics against anaphylaxis should probably target oxidative stress and mitochondria, in order to decrease anaphylaxis-induced systemic and major organ deleterious effects.
过敏反应是一种由活性介质大量释放引起的过敏反应，可导致过敏性休克（AS），这是过敏反应最严重且可能危及生命的形式。然而，对其病理生理学的理解以支持新疗法仍有待改进。我们进行了一项系统综述，评估了过敏反应、肥大细胞代谢和脱颗粒过程中线粒体和氧化应激的作用以及复杂的细胞相互作用。在介绍了过敏反应的主要特征、氧化还原/抗氧化平衡和线粒体功能之后，我们将本综述的重点放在线粒体和氧化应激在过敏反应中的作用上。然后，我们讨论了变应原刺激肥大细胞后氧化应激和线粒体的作用，导致脱颗粒，以进一步阐明作用机制途径。最后，我们考虑了利用这些发现进行潜在治疗干预以治疗过敏反应。实验研究主要评估了过敏性休克期间心肌细胞的代谢。心脏功能障碍与左心室线粒体损伤和脂质过氧化有关。评估免疫球蛋白E（IgE）或非IgE刺激后体外肥大细胞脱颗粒的研究表明，线粒体呼吸复合体完整性和膜电位对肥大细胞脱颗粒至关重要。抗原刺激会增加烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶和线粒体产生的活性氧（ROS），导致肥大细胞脱颗粒。此外，肥大细胞活化涉及线粒体形态变化以及线粒体向胞吐位点附近的细胞表面移位。有趣的是，给予抗氧化剂可通过降低ROS水平减少脱颗粒。总之，这些结果突出了氧化应激和线粒体在过敏反应和肥大细胞脱颗粒过程中的关键作用。针对过敏反应的新疗法可能应针对氧化应激和线粒体，以减少过敏反应引起的全身和主要器官的有害影响。
