vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-78-4-2vestnik-bio-msu-1242Research ArticleОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕRESEARCH ARTICLEУчастие митоген-активируемых протеинкиназ р38 и ERK1/2, а также протеинкиназы В Akt1/2 в образовании нейтрофильных внеклеточных ловушекInvolvement of mitogen-activated protein kinases p38 and ERK1/2 as well as protein kinase B Akt1/2 in the formation of neutrophil extracellular trapshttps://orcid.org/0000-0001-5233-9338ВоробьеваН. В.VorobjevaN. V.

Воробьева Нина Викторовна – канд. биол. наук, ст. науч. сотр. кафедры иммунологии биологического факультета МГУ

nvvorobjeva@mail.ruМосковский государственный университет имени М.В. ЛомоносоваРоссияLomonosov Moscow State UniversityRussian Federation202329122023784243–249Copyright © Воробьева Н.В., 20232023Воробьева Н.В.Vorobjeva N.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/1242

Нейтрофилы высвобождают деконденсированный ядерный хроматин или нейтрофильные внеклеточные ловушки (NET, Neutrophil Extracellular Trap) в ответ на большое количество разнообразных физиологических стимулов с целью защиты хозяина от патогенов. Однако как было недавно установлено, NET играют также важную роль в патогенезе аутоиммунных, воспалительных и онкологических заболеваний. В этой связи понимание молекулярных механизмов, лежащих в основе образования NET и ведущих, как правило, к гибели нейтрофилов (NETоз), крайне важно для обеспечения контроля за аберрантным выбросом хроматина. Митоген-активируемые протеинкиназы (MAP-киназы) участвуют в разнообразных функциях клеток, таких как окислительный взрыв, хемотаксис, дегрануляция, адгезия и апоптоз, однако их роль в NETозе исследовалась недостаточно. У нейтрофилов человека описаны три семейства MAP-киназ – p38, ERK1/2 и JNK. В нашей работе было исследовано участие p38, ERK1/2, а также протеинкиназы В Akt1/2 в окислительном взрыве и NETозе с использованием ингибиторного анализа. Мы показали, что MAP-киназа р38 и протеинкиназа В Akt1/2 активируются при стимуляции окислительного взрыва и NETоза кальциевым ионофором иономицином. Вместе с тем эти киназы не принимают участия в окислительном взрыве, индуцированном миметиком диацилглицерола форбол 12-миристат 13-ацетатом (ФМА), но участвуют в ФМА-индуцированном NETозе.

Neutrophils release decondensed nuclear chromatin or Neutrophil Extracellular Traps (NETs) in response to a great number of physiological stimuli to protect the host from pathogens. However, NETs have recently been shown to play an important role in the pathogenesis of autoimmune, inflammatory, and malignant diseases. Therefore, understanding the molecular mechanisms underlying NETs formation, usually leading to the neutrophil death (NETosis), is extremely important to control the aberrant release of chromatin. Mitogen-activated protein kinases (MAP-kinases) are involved in various cellular functions such as oxidative burst, chemotaxis, degranulation, adhesion, and apoptosis, but their role in NETosis is not well understood. Three families of MAP-kinases, p38, ERK1/2, and JNK, have been described in human neutrophils, and we investigated the contribution of p38, ERK1/2, and protein kinase B Akt1/2 in oxidative burst and NETosis using inhibitory analysis. We have shown that MAP-kinase p38 as well as protein kinase B Akt1/2 are activated upon stimulation of oxidative burst and NETosis with calcium ionophore ionomycin. However, these kinases are not involved in the oxidative burst induced by diacylglycerol mimetic phorbol 12-myristate 13-acetate (PMA) but are involved in PMA-induced NETosis.

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