最近的研究表明肥大细胞(MC)在2019年冠状病毒病(COVID-19)病理中的潜在作用。然而,对MCs的激活及其蛋白酶的参与的准确描述仍然缺失。本研究的目的是进一步揭示MC及其蛋白酶(糜蛋白酶,胰蛋白酶,和羧肽酶A3(CPA3))在COVID-19患者肺损伤发展中的作用。这项研究包括55例死于COVID-19的患者和30例死于外因的对照。进行肺实质的组织学分析以评估MC的蛋白酶谱和脱粒活性。此外,我们分析了一般的血液检查,凝血图,和C反应蛋白.COVID-19患者肺部类胰蛋白酶阳性MCs(Try-MCs)的含量高于对照组,但它们的脱颗粒活性较低。糜蛋白酶阳性MCs(Chy-MCs)指标明显低于对照组,而COVID-19患者的CPA3阳性MC(CPA3-MC)含量及其脱颗粒活性较高。此外,我们已经证明了Try-MC含量之间存在相关性(正/负),Chy-MC,和CPA3-MCs在不同状态的脱颗粒和存在(共同相邻/单一)和水平的各种免疫细胞(嗜中性粒细胞,嗜酸性粒细胞,嗜碱性粒细胞,和单核细胞)和其他重要标志物(血液血红蛋白,活化部分凝血活酶时间(aPTT),国际标准化比率(INR),和纤维蛋白原)。因此,已确定的模式提示MC及其蛋白酶参与COVID-19发病机制的众多机制,以及它们对炎症过程和凝血状态的影响.同时,这个问题需要在更大的患者群体中进一步研究,这将为COVID-19患者使用作用于这一发病环节的药物治疗肺损伤开辟可能性。
Recent studies suggested the potential role of mast cells (MCs) in the pathology of coronavirus disease 2019 (COVID-19). However, the precise description of the MCs\' activation and the engagement of their proteases is still missing. The objective of this study was to further reveal the importance of MCs and their proteases (chymase, tryptase, and carboxypeptidase A3 (CPA3)) in the development of lung damage in patients with COVID-19. This study included 55 patients who died from COVID-19 and 30 controls who died from external causes. A histological analysis of the lung parenchyma was carried out to assess the protease profiles and degranulation activity of MCs. In addition, we have analyzed the general blood test, coagulogram, and C-reactive protein. The content of tryptase-positive MCs (Try-MCs) in the lungs of patients with COVID-19 was higher than in controls, but their degranulation activity was lower. The indicators of chymase-positive MCs (Chy-MCs) were significantly lower than in the controls, while the content of CPA3-positive MCs (CPA3-MCs) and their degranulation activity were higher in patients with COVID-19. In addition, we have demonstrated the existence of correlations (positive/negative) between the content of Try-MCs, Chy-MCs, and CPA3-MCs at different states of their degranulation and presence (co-adjacent/single) and the levels of various immune cells (neutrophils, eosinophils, basophils, and monocytes) and other important markers (blood hemoglobin, activated partial thromboplastin time (aPTT), international normalized ratio (INR), and fibrinogen). Thus, the identified patterns suggest the numerous and diverse mechanisms of the participation of MCs and their proteases in the pathogenesis of COVID-19, and their impact on the inflammatory process and coagulation status. At the same time, the issue requires further study in larger cohorts of patients, which will open up the possibility of using drugs acting on this link of pathogenesis to treat lung damage in patients with COVID-19.