Russian Journal of Infection and ImmunityRussian Journal of Infection and ImmunityИнфекция и иммунитет2220-76192313-7398SPb RAACI71210.15789/2220-7619-2019-1-9-38REVIEWSОБЗОРЫUnknownNeutrophil as a multifunctional relay in immune systemНейтрофил как «многофункциональное устройство» иммунной системыDolgushinI. I.ДолгушинИ. И.
Russian Federation

PhD, MD (Medicine), Professor, President of South-Ural State Medical University, Head of the Department of Microbiology, Virology, Immunology and Clinical Laboratory Diagnostics, South-Ural State Medical University.

454092, Chelyabinsk, Vorovskogo str., 64.

Долгушин Илья Ильич - доктор медицинских наук, профессор, Президент ФГБОУ ВО ЮУГМУ Минздрава России, заведующий кафедрой микробиологии, вирусологии, иммунологии и клинической лабораторной диагностики.

454092, Челябинск, ул. Воровского, 64.

xxx@mail.ruMezentsevaE AМезенцеваЕ. А.
Russian Federation

PhD (Medicine), Associate Professor, Department of Microbiology, Virology, Immunology and Clinical Laboratory Diagnostics, South-Ural State Medical University.

454092, Chelyabinsk, Vorovskogo str., 64.

Кандидат медицинских наук, доцент кафедры микробиологии, вирусологии, иммунологии и клинической лабораторной диагностики ФГБОУ ВО ЮУГМУ Минздрава России.

454092, Челябинск, ул. Воровского, 64.

xxx@mail.ruSavochkinaA YuСавочкинаА. Ю.
Russian Federation

Albina Yu. Savochkina - PhD, MD (Medicine), Associate Professor, Professor of the Department of Microbiology, Virology, Immunology and Clinical Laboratory Diagnostics, South-Ural State Medical University.

454092, Chelyabinsk, Vorovskogo str., 64.

Phone: +7 (912) 772-58-06.

Савочкина Альбина Юрьевна - доктор медицинских наук, доцент, профессор кафедры микробиологии, вирусологии, иммунологии и клинической лабораторной диагностики ФГБОУ ВО ЮУГМУ Минздрава России.

alina7423@mail.ruKuznetsovaE KКузнецоваЕ. К.
Russian Federation

PhD (Medicine), Assistant Professor, Department of Skin and Sexually Transmitted Diseases, Orenburg State Medical University.

Кандидат медицинских наук, ассистент кафедры кожных и венерических болезней.

xxx@mail.ruSouth-Ural State Medical University of the Ministry of Healthcare of the Russian FederationЮжно-Уральский государственный медицинский университет МЗ РФOrenburg State Medical University of the Ministry of Healthcare of the Russian FederationОренбургский государственный медицинский университет МЗ РФ19052019919380307201822032019Copyright ©; 2019, Dolgushin I.I., Mezentseva E.A., Savochkina A.Y., Kuznetsova E.K.Copyright ©; 2019, Долгушин И.И., Мезенцева Е.А., Савочкина А.Ю., Кузнецова Е.К.2019Dolgushin I.I., Mezentseva E.A., Savochkina A.Y., Kuznetsova E.K.Долгушин И.И., Мезенцева Е.А., Савочкина А.Ю., Кузнецова Е.К.https://creativecommons.org/licenses/by/4.0https://iimmun.ru/iimm/article/view/712

Over the last two or three decades, a concept regarding functional capacities of neutrophilic granulocytes has been remarkably extended owing to new technologies. Neutrophil-related effector potential against infectious agents, including phagocytosis, production of reactive oxygen and nitrogen species, degranulation coupled with the released multiple enzymes and antimicrobial peptides, and the extracellular trap formation have been studied in detail. In particular, it was found that many of the factors used by neutrophils to directly destroy pathogens also exert regulatory effects on other immune cells as well as on neutrophils in an autocrine manner. In addition, activated neutrophils are able to de novo synthesize a range of biologically active molecules. Neutrophil-related immunoregulatory effects on macrophages, dendritic cells, T-lymphocytes and B-lymphocytes may be mediated both via direct intercellular contacts and indirectly through production of cytokines and other biologically active mediators. Ambiguous proactive and suppressive neutrophil-related effects on immune cells evidence about their important role played both in homeostasis and diverse pathologies, particularly in developing malignant tumors. Diverse, even opposing impact exhibited by neutrophilic granulocytes on immune cells and cells in non-lymphoid tissues, point at their functional plasticity and, probably, heterogeneity. Upon that, modality of effects elicited by neutrophils largely depends on surrounding microenvironment while they exit from the circulation. Widely considered as an inf lammatory response inducer, neutrophils are able to simultaneously trigger mechanisms facilitating restriction and resolution of inf lammatory reaction. Using intravital microscopy in animal models, it allowed to discover that neutrophils are able to re-enter circulation after exiting into the extravascular space, thereby challenging a classical concept about a unidirectional neutrophil migration from the blood vessels to body tissue. In addition, evidence that neutrophils can serve as antigen-presenting cells for T cells under certain conditions and are recruited from inf lammatory sites to draining lymph nodes were also obtained. Although a body of the data were obtained in vitro or in animal models, which therefore require to be further examined and verified, it may be unequivocally acknowledged that a neutrophil-related impact is not only limited to innate immunity.

За последние 2–3 десятилетия благодаря использованию новых технологий было значительно расширено представление о спектре функциональных возможностей нейтрофильных гранулоцитов. Детально изучен их эффекторный потенциал в отношении инфекционных агентов, включающий фагоцитоз, продукцию активных форм кислорода и азота, дегрануляцию с высвобождением многочисленных ферментов и антимикробных пептидов, образование внеклеточных ловушек. При этом установлено, что многие их тех факторов, которые нейтрофилы используют для прямого уничтожения патогенов, оказывают регулирующее влияние в отношении других клеток иммунной системы и самих нейтрофилов. Кроме того, при активации нейтрофилы способны синтезировать ряд биологически активных молекул de novo. Реализация иммунорегуляторного влияния нейтрофилов в отношении макрофагов, дендритных клеток, Т-лимфоцитов и В-лимфоцитов может происходить как путем прямого межклеточного контакта, так и опосредовано через продукцию цитокинов и других биологически активных медиаторов. Амбивалентное — как хелперное, так и супрессорное — воздействие нейтрофилов на клетки иммунной системы свидетельствует об их важной роли как в условиях гомеостаза, так и при различных видах патологии, в частности при развитии злокачественных опухолей. Способность нейтрофильных гранулоцитов проявлять разнообразные, порой даже антагонистические варианты воздействия на иммунные клетки и клетки других тканей, свидетельствует об их функциональной пластичности и, вероятно, гетерогенности. При этом вектор активности, проявляемой нейтрофилами, во многом зависит от того микроокружения, в котором они оказываются, выходя из периферического кровотока. Традиционно считаясь индукторами воспалительной реакции, нейтрофилы демонстрируют способность параллельно включать механизмы, способствующие ограничению и разрешению воспаления. Благодаря интравитальной микроскопии в моделях на животных установлена способность нейтрофилов возвращаться в кровоток после выхода во внесосудистое пространство, что бросает вызов классической концепции однонаправленности миграции нейтрофилов из сосудистого русла в ткани. Также получены доказательства, что в определенных условиях нейтрофилы могут проявлять себя как антиген-презентирующие клетки по отношению к Т-лимфоцитам и рекрутироваться из сайтов воспаления в дренирующие лимфатические узлы. И хотя многие данные получены в условиях in vitro или в моделях на животных и поэтому требуют дополнительного изучения и подтверждения, однозначно можно констатировать, что влияние нейтрофилов не ограничивается рамками системы врожденного иммунитета.

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