RUDN Journal of MedicineRUDN Journal of MedicineВестник Российского университета дружбы народов. Серия: Медицина2313-02452313-0261Peoples’ Friendship University of Russia named after Patrice Lumumba (RUDN University)5206510.22363/2313-0245-2025-30-3-301-313JZDMMQCELL BIOLOGYКЛЕТОЧНАЯ БИОЛОГИЯReview ArticleProgrammed neutrophil death in immunothrombosisЗапрограммированная гибель нейтрофилов при иммунотромбозеhttps://orcid.org/0000-0002-8701-72132685-9578PlekhovaNatalya G.ПлеховаН. Г.plekhova.ng@tgmu.ruhttps://orcid.org/0000-0002-2719-36291469-9086MikhailovAlexander O.МихайловА. О.plekhova.ng@tgmu.ruhttps://orcid.org/0009-0009-0318-06616076-0443TsvetovNikolay V.ЦветовН. В.plekhova.ng@tgmu.ruhttps://orcid.org/0000-0001-7571-07503863-4021VoronovaAnastasia N.ВороноваА. Н.plekhova.ng@tgmu.ruPacific State Medical UniversityТихоокеанский государственный медицинский университет30082026303CELL BIOLOGYКЛЕТОЧНАЯ БИОЛОГИЯ30131331082026Copyright ©; 2026, Plekhova N.G., Mikhailov A.O., Tsvetov N.V., Voronova A.N.Copyright ©; 2026, Плехова Н.Г., Михайлов А.О., Цветов Н.В., Воронова А.Н.2026Plekhova N.G., Mikhailov A.O., Tsvetov N.V., Voronova A.N.Плехова Н.Г., Михайлов А.О., Цветов Н.В., Воронова А.Н.https://creativecommons.org/licenses/by-nc/4.0https://journals.rudn.ru/medicine/article/view/52065

Relevance. Understanding the fundamental mechanisms of immunothrombosis is essential for developing effective treatments and prevention of thrombotic disorders. This review aims to summarize the current knowledge on the role of programmed neutrophil death in the molecular and cellular mechanisms underlying immunothrombosis, as well as to demonstrate how dysregulation of hemostasis initiated by neutrophil death is associated with various pathological conditions. Based on a search of the electronic scientific databases Google Scholar, PubMed (MEDLINE), Scopus, and Web of Science using keywords and their combinations, with the methodological quality assessed using the AMSTAR 2 software, the role of neutrophil death in the development of immunothrombosis is presented. The review describes the types of programmed neutrophil cell death, namely apoptosis, pyroptosis, necroptosis, ferroptosis, and neutrophil extracellular traps (NETs), along with their molecular triggers and mechanisms. A modern concept of immunothrombosis pathogenesis is presented, demonstrating the involvement of hemostatic proteins, platelets, and proinflammatory cells in its pathogenesis and taking into account the complex relationship between hemostasis and inflammation. Each type of programmed neutrophil death is shown to be involved in the development of immunothrombosis. In addition, the review presents data on therapeutic strategies employing immunometabolic regulators and NET inhibitors, which potentially can attenuate immunothrombotic activity without affecting hemostasis. Such treatment approaches offer advantages for managing patients with various thrombo-inflammatory conditions. Conclusion. Overall, the data demonstrate that neutrophil apoptosis has an antithrombotic effect, whereas other types of programmed cell death promote thrombus formation and vascular events. The latter differ in that they require specific triggers: a cytokine storm for pyroptosis, the release of death-associated molecular patterns (DAMPs) for necroptosis, and oxidative stress for ferroptosis. These types of cell death are unified by their capacity to initiate NET formation, thereby providing a trigger framework for the development of severe thrombotic complications.

Понимание основных механизмов иммунотромбоза необходимо для разработки эффективных методов лечения и профилактики тромботических нарушений. Цель обзора - изложить существующие знания о роли запрограммированной гибели нейтрофилов в молекулярных и клеточных механизмах развития иммунотромбоза, а также представить, каким образом дизрегуляция гемостаза, инициированная смертью этих клеток, связана с различными патологическими состояниями. На основании поиска работ в электронных научных базах данных Google Scholar, PubMed (MEDLINE), Scopus и Web of Science по ключевым словам и их сочетаниям с использованием программы AMSTAR 2 представлена роль гибели нейтрофилов в развитии иммунотромбозов. Изложены данные о типах запрограммированной гибели нейтрофилов, а именно апоптозе, пироптозе, некроптозе, ферроптозе и нейтрофильных внеклеточных ловушках (НВЛ), их молекулярных триггерах и механизмах. Представлена современная концепция патогенеза иммунотромбоза, которая демонстрирует вовлеченность в его патогенез гемостатических белков, тромбоцитов, провоспалительных клеток и учитывает сложную связь между гемостазом и воспалением. По каждому из типов запрограммированной гибели нейтрофилов показано участие в развитии иммунотромбоза. Наряду с этим, изложены сведения о терапевтических стратегиях с использованием иммунометаболических регуляторов и ингибиторов НВЛ, которые потенциально могут ослабить иммунотромботическую активность, не влияя на гемостаз. Такие методы лечения имеют преимущества для лечения пациентов при многих тромбовоспалительных состояниях. Выводы. В целом, продемонстрированные данные указывают, что апоптоз нейтрофилов обладает противотромботическим эффектом, тогда как остальные типы запрограммированной гибели способствуют развитию тромбов и сосудистых катастроф. К отличиям последних относятся специфические триггеры, а именно, для пироптоза цитокиновый шторм, для некроптоза выброс молекулярных паттернов смерти и для ферроптоза окислительный стресс. Объединяет указанные типы гибели способность запускать НВЛ, результатом чего является формирование триггерной основы развития тяжелых тромботических осложнений.

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