Аннотация
Нейтрофильные гранулоциты – это наиболее многочисленная группа миелоидных клеток, обеспечивающих защиту организма путем производства активных форм кислорода и хлора, фагоцитоза патогенов и мертвых клеток, продукции хемокинов и цитокинов, и выброса внеклеточных нейтрофильных ловушек – NETs (Neutrophil Extracellular Traps), состоящих
из хроматина и гранул, способных связывать и уничтожать микроорганизмы. При иммуновоспалительных ревматических
заболеваниях (ИВРЗ) образование NETs приводит к повреждению органов и тканей, что сопровождается воспалением и
тромбообразованием. Этот процесс обусловлен высвобождением большого количества белков и ферментов, активирующих
макрофаги и лимфоциты, а также аутоантигенов, что стимулирует образование аутоантител. Повышенная продукция
миелопероксидазы (МПО) и протеиназы – 3 (ПР-3) имеет важное значение в патогенезе системных васкулитов, нуклеиновые кислоты и молекулы ДНК являются аутоантигенами при системной красной волчанке (СКВ), цитруллинированные гистоны можно рассматривать как неоэпитопы, вызывающие формирование антител к цитруллинированным белкам (АЦБ)
при ревматоидном артрите (РА).
Нетоз могут вызывать антитела, иммунные комплексы, цитокины, хемокины, микрокристаллы. В настоящее время описаны две принципиально различающиеся формы нетоз: классический или суицидальный нетоз, который приводит к гибели
клетки, и прижизненный или витальный, при котором клетка не погибает и сохраняет многие эффекторные функции.
Учитывая большой вклад нетоза в патогенезе ИВРЗ в литературе широко обсуждаются практические вопросы оценки нетоза у различных групп пациентов. Среди методов можно выделить микроскопию, мммуноферментный анализ продуктов
нетоза, а также метод многоцветной проточной цитометрии, который позволяет выявлять основные компоненты NETs
в цельной крови. Эта методика позволяет быстро и надежно оценить несколько тысяч клеток на образец и не зависит от
потенциальной ошибки наблюдателя — двух основных ограничений микроскопической количественной оценки. Использование
цитометрии облегчает прямое обнаружение in vivo циркулирующих NETs в образцах крови.
Целью публикации является обобщение и анализ наиболее важных исследований, касающихся роли нетоза нейтрофилов в
патогенезе ИВРЗ, а также обсуждаются перспективные направления лабораторной диагностики нетоза. Был проведен
исчерпывающий поиск в базах данных MEDLINE (через PubMed), с использованием MESH (medical subjects headings) терминологии и ключевых слов, включая ревматоидный артрит, системная красная волчанка, системные васкулиты, патогенез
заболевания, нетоз, многоцветная проточная цитометрия, микроскопия, мммуноферментный анализ.
Annotation
Neutrophil granulocytes are the most numerous group of myeloid cells that provide protection to the body by producing reactive oxygen and chlorine species, phagocytosis of pathogens and dead cells, production of chemokines and cytokines, and release of
NETs (Neutrophil Extracellular Traps), consisting of chromatin and granules , capable of binding and destroying microorganisms. In
systemic autoimmune rheumatic diseases (SARDs), the formation of NETs leads to damage to organs and tissues, which is accompanied
by inflammation and thrombus formation. This process is caused by the release of a large number of proteins and enzymes that activate
macrophages and lymphocytes, as well as autoantigens, which stimulates the formation of autoantibodies. Increased production of
myeloperoxidase (MPO) and proteinase 3 (PR-3) is important in the pathogenesis of systemic vasculitis, nucleic acids and DNA
molecules are autoantigens in systemic lupus erythematosus (SLE), citrullinated histones can be considered as neoepitopes that cause
the formation of antibodies to citrullinated proteins (ACPA) in rheumatoid arthritis (RA).
Netosis can be caused by antibodies, immune complexes, cytokines, chemokines, and microcrystals. Currently, two fundamentally
different forms of NETosis have been described: classic or suicidal NETosis, which leads to cell death, and intravital or vital, in which
the cell does not die and retains many effector functions.
Considering the large contribution of NETosis in the pathogenesis of SARDs, practical issues of assessing NETosis in various groups
of patients are widely discussed in the literature. Methods include microscopy, enzyme-linked immunosorbent assay of NET products,
and multicolor flow cytometry, which allows the identification of the main components of NETs in whole blood. This technique allows
rapid and reliable assessment of several thousand cells per sample and is not subject to potential observer error, two major limitations
of microscopic quantification. The use of cytometry facilitates the direct in vivo detection of circulating NETs in blood samples.
The purpose of the publication is to summarize and analyze the most important studies concerning the role of neutrophil NETosis in
the pathogenesis of SARDs, and also to discuss promising directions for laboratory diagnosis of NETosis. An exhaustive search was
conducted in MEDLINE databases (via PubMed), using MESH (medical subject headings) terminology and keywords, including
rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitides, disease pathogenesis, NETosis, multicolor flow cytometry,
microscopy, enzyme-linked immunosorbent assay.
Key words: systemic autoimmune rheumatic diseases; NETosis; pathogenesis; multicolor flow cytometry; review
Список литературы
Л И Т Е Р А Т У Р А ( П П . 2 — 2 0 , 2 3 — 7 6 С М .
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