Журнал микробиологии, эпидемиологии и иммунобиологии. 2021; 98: 567-578
Роль плазменного ингибитора сериновых лейкоцитарных протеиназ в защите организма от COVID-19
Кравцов А. Л., Бугоркова С. А.
https://doi.org/10.36233/0372-9311-160Аннотация
Пандемия COVID-19 продолжается, нанося колоссальный ущерб населению и мировой экономике. По мере изучения COVID-19 появляются новые данные относительно риска тяжёлого течения коронавирусной инфекции у пациентов с дефицитом α1-антитрипсина (ААТ). ААТ — основной ингибитор и ключевой эндогенный регулятор активности сериновых лейкоцитарных протеиназ, высвобождаемых из гранул активированных нейтрофилов на поверхность клеток и во внеклеточное пространство. Установлено, что число случаев тяжёлого течения и летального исхода COVID-19 на территориях 68 стран мира коррелирует с частотой распространения среди населения этих стран мутации в гене протеиназного ингибитора, при которой концентрация ААТ в плазме крови человека в 10 раз ниже нормы. Всё это способствует пересмотру ряда положений патогенеза и терапии COVID-19.
В обзоре представлен анализ литературы о роли ингибитора сериновых лейкоцитарных протеиназ в защите организма от COVID-19. Рассмотрено участие ААТ в ингибировании процесса проникновения SARS-CoV-2 в эпителиальные клетки дыхательных путей, в защите эндотелия сосудов, белков плазмы крови и эластина лёгочной ткани от повреждающего действия лейкоцитарной эластазы, высвобождаемой при дегрануляции нейтрофилов и формировании нейтрофильных внеклеточных ловушек. Показана роль ААТ в супрессии воспаления посредством ограничения секреции в кровь провоспалительных цитокинов и нейтрофильных внеклеточных ловушек. Детализированы отдельные звенья патогенеза новой коронавирусной инфекции, что позволит пересмотреть стратегию снижения рисков тяжёлого течения COVID-19.
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Journal of microbiology, epidemiology and immunobiology. 2021; 98: 567-578
The role of plasma serine leukocyte proteinase inhibitor in the body's defense against COVID-19
Kravtsov A. L., Bugorkova S. A.
https://doi.org/10.36233/0372-9311-160Abstract
The COVID-19 pandemic continues, causing colossal damage to the population and the global economy. As COVID-19 is studied, new data are emerging regarding the risk of severe coronavirus infection in patients with α1-antitrypsin deficiency. α1 -Antitrypsin is the main inhibitor and key endogenous regulator of the serine leukocyte proteinase activitry released from the granules of activated neutrophils to the cell surface and into the extracellular space. It has been established that the number of cases of severe course and death of COVID-19 in the territories of 68 countries of the world correlates with the frequency of the spread of mutations in the proteinase inhibitor gene among the population of these countries, at which the concentration of α1-antitrypsin in the human blood plasma is 10 times lower than normal. All this contributes to the revision of a number of provisions of the pathogenesis and therapy of a new coronavirus infection.
The review presents an analysis of the literature on the role of an inhibitor of serine leukocyte proteinases in protecting the body from COVID-19. The participation of α1-antitrypsin in the inhibition of SARS-CoV-2 penetration into the respiratory tract epithelial cells, in the protection of the vascular endothelium, blood plasma proteins and elastin of the lung tissue from the damaging effect of leukocyte elastase released during neutrophil degranulation and the formation of neutrophil extracellular traps (NETs) is considered. The role of a1-antitrypsin in suppressing inflammation by limiting the secretion of proinflammatory cytokines and neutrophil extracellular traps into the blood has been shown. The individual links in the pathogenesis of the new coronavirus infection have been detailed, which will allow revising the strategy for reducing the risks of severe course of COVID-19.
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