vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biologyvestnik-bio-msu-1133Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEРоль изоформ протеинкиназы С в образовании нейтрофильных внеклеточных ловушекThe role of protein kinase C isoforms in the formation of neutrophil extracellular trapshttps://orcid.org/0000-0001-5233-9338ВоробьеваН. В.VorobjevaN. V.

канд. биол. наук, ст. науч. сотр.

Тел.: 8-495-939-46-46

Россия, 119234, г. Москва, Ленинские горы, д. 1, стр. 12 

1–12 Leninskie Gory, Moscow, 119234, Russia 

nvvorobjeva@mail.ruВахлярскаяС. С.VakhlyarskayaS. S.

 канд. мед. наук, врач-аллерголог-иммунолог

Тел.: 8-800-555-04-94

Россия, 119571, г. Москва, Ленинский проспект, д. 117 

117 Leninsky prospect, Moscow, 119571, Russia 

vahlyarskaya@mail.ruЧернякБ. В.ChernyakB. V.

 докт. биол. наук, проф., зав. лаб. биоэнергетики клетки

Тел.: 8-495-939-55-50 

Россия, 119992, г. Москва, Ленинские горы, д. 1, стр. 40 

1–40 Leninskie Gory, Moscow, 119992, Russia 

bchernyak1@gmail.comКафедра иммунологии, биологический факультет, Московский государственный университет имени М.В. ЛомоносоваРоссияDepartment of Immunology, Biology Faculty, Lomonosov Moscow State UniversityRussian FederationОтделение клинической иммунологии и ревматологии, Российская детская клиническая больница, Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияRussian Children’s Clinical Hospital, N.I. Pirogov Russian National Research Medical UniversityRussian FederationНаучно-исследовательский институт физико-химической биологии имени А.Н. Белозерского, Московский государственный университет имени М.В. ЛомоносоваРоссияA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State UniversityRussian Federation202215062022772112–121Copyright © Воробьева Н.В., Вахлярская С.С., Черняк Б.В., 20222022Воробьева Н.В., Вахлярская С.С., Черняк Б.В.Vorobjeva N.V., Vakhlyarskaya S.S., Chernyak B.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1133

Нейтрофилы высвобождают деконденсированный ядерный хроматин, или нейтрофильные внеклеточные ловушки (NET, от Neutrophil Extracellular Trap) в ответ на большое количество разнообразных физиологических и фармакологических стимулов. Однако, кроме защиты хозяина от инфекции, NET играют важную роль в патогенезе различных аутоиммунных, воспалительных и злокачественных заболеваний. В этой связи понимание молекулярных механизмов образования NET, ведущее, как правило, к гибели нейтрофилов (НЕТоз), крайне важно для обеспечения контроля последствий аберрантного или избыточного выброса хроматина. Протеинкиназа C (PKC, protein kinase C) представляет собой серин/треониновую киназу, которая участвует в разнообразных функциях нейтрофилов, однако ее участие в НЕТозе изучено недостаточно. Поскольку у нейтрофилов человека описано пять изоформ РКС (α, βI, βII, δ и ζ), в нашей работе был изучен их вклад в НЕТоз и окислительный взрыв с использованием ингибиторного анализа. Используя специфические ингибиторы изоформ PKC, мы показали, что PKCβ, PKCδ и PKCζ участвуют в окислительном взрыве и НЕТозе, индуцированном кальциевым ионофором A23187, тогда как PKCβ участвует в окислительном взрыве и НЕТозе при активации клеток миметиком диацилглицерола форбол-12-миристат-13-ацетатом.

Neutrophils release decondensed nuclear chromatin or neutrophil extracellular traps (NET) in response to a great number of physiological and pharmacological stimuli. However, apart from the host defensive function, NETs play an essential role in the pathogenesis of various autoimmune, inflammatory, and malignant diseases. Therefore, understanding the molecular mechanisms of NET formation, usually leading to the neutrophil death (NETosis), is important to control the consequences of aberrant or excessive NET release. Protein kinase C (PKC) is a serine/threonine kinase that is involved in a variety of neutrophil functions, but its role in NETosis is not well understood. Since five PKC isoforms (α, βI, βII, δ, and ζ) have been described in human neutrophils, we studied their contribution to NETosis and oxidative burst using inhibitory analysis. Using specific PKC isoform inhibitors, we have shown that PKCβ, PKCδ, and PKCζ are involved in the oxidative burst and NETosis activated by calcium ionophore A23187, while PKCβ is involved in the oxidative burst and NETosis upon cell activation by diacylglycerol mimetic phorbol 12-myristate 13-acetate.

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The authors declare that there are no conflicts of interest present.