Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children87610.24287/1726-1708-2024-23-2-222-230LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫIntracellular signaling involved in the programmed neutrophil cell death leading to the release of extracellular DNA traps in thrombus formationВнутриклеточная сигнализация при феномене запрограммированной гибели нейтрофилов с появлением внеклеточных ДНК-ловушек при тромбообразованииhttps://orcid.org/0000-0003-4720-7319SveshnikovaA. N.СвешниковаА. Н.
Russian Federation

Anastasia N. Sveshnikova, Dr. Sci. in Physics and Mathematics, Head of the Laboratory of Cellular Biology  and Translational Medicine of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

1 Samory Mashela St., Moscow 117997, Russia

Свешникова Анастасия Никитична, д-р физ.-мат. наук, заведующая лабораторией клеточной биологии и трансляционной медицины ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева»

117997, Москва, ул. Саморы Машела, 1

a.sveshnikova@physics.msu.ruhttps://orcid.org/0009-0000-4828-4063AdamanskayaE. A.АдаманскаяЕ. А.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2762-5460KorobkinaYu.-D. D.КоробкинаЮ.-Д. Д.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-8128-7757PanteleevM. A.ПантелеевМ. А.
Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава РоссииM.V. Lomonosov Moscow State UniversityФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»Center for Theoretical Problems of Physical and Chemical Pharmacology, Russian Academy of SciencesФГБУН «Центр теоретических проблем физико-химической фармакологии» РАН0807202423222223023072024Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/876

The formation of extracellular DNA traps by neutrophils, or NETs (neutrophil extracellular traps) plays an essential role in many pathological processes related to hematological, oncological, and immunological diseases. This mechanism of the programmed cell death of neutrophils and other leukocytes appears to be also involved in the pathogenesis of thrombosis and thrombotic complications of a variety of disorders. In this review, we discuss the pathways of intracellular signaling leading to neutrophil activation in thrombosis and hemostasis. Even though the biochemical reactions in a cell are quite well investigated, the regulation of activity of specific proteins involved in NETosis, such as NADPH oxidase (NOX) and protein-arginine deiminase (PAD4), requires further investigation. Current approaches to the pharmacological modulation of NETosis are also specifically addressed here.

Формирование внеклеточных ДНК-ловушек нейтрофилов (NET-оз) является важной составляющей многих патологических процессов, относящихся к областям современной гематологии, онкологии и иммунологии. Этот механизм запрограммированной клеточной смерти нейтрофилов и других лейкоцитов оказался вовлечен и в патогенез тромбозов и тромботических осложнений многих заболеваний. В данном обзоре мы рассматриваем пути внутриклеточной сигнализации, ведущие к активации нейтрофилов в условиях тромбоза и гемостаза. Несмотря на то, что биохимические реакции в клетке изучены достаточно хорошо, в NET-оз оказываются вовлечены такие специфические белки, как NADPH-оксидаза (NOX) и пептидил-аргинин деиминаза (PAD4), регуляция активности которых изучена недостаточно. Отдельно рассматриваются существующие подходы к фармакологической модуляции NET-оза.

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