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Involvement of Mitogen-Activated Protein Kinases p38 and ERK1/2, as well as Protein Kinase B Akt1/2, in the Formation of Neutrophil Extracellular Traps

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Abstract

Neutrophils release decondensed nuclear chromatin or neutrophil extracellular trap (NETs) in response to a large number of different physiological stimuli in order to protect the host from the pathogens. However, as it has been recently established, NETs play an important role in the pathogenesis of autoimmune, inflammatory, and oncological diseases. In this regard, understanding molecular mechanisms underlying the formation of NETs and leading, as a rule, to the death of neutrophils (NETosis) is extremely important to provide a control of aberrant chromatin release. Mitogen-activated protein kinases (MAP kinases) are involved in diverse cellular functions, such as oxidative burst, chemotaxis, degranulation, adhesion, and apoptosis; however, their role in NETosis was not sufficiently studied. Three families of MAP kinases were described in human neutrophils, including p38, ERK1/2, and JNK. In our work, the involvement of p38, ERK1/2, as well as protein kinase B Akt1/2, in the oxidative burst and NETosis was studied using an inhibitory analysis. We demonstrated that p38 MAP kinase and protein kinase B Akt1/2 are activated upon stimulation of the oxidative burst and NETosis by calcium ionophore ionomycin. At the same time, 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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Funding

The research was carried out within the framework of the Scientific Project of the State Order of the Government of Russian Federation to Moscow State University no. 121042600047-9 and Interdisciplinary Scientific and Educational School of Moscow University “Molecular Technologies of the Living Systems and Synthetic Biology.”

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  1. Faculty of Biology, Moscow State University, 119234, Moscow, Russia

    N. V. Vorobjeva

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Correspondence to N. V. Vorobjeva.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

This study was approved by the local ethics committee of the Russian Children’s Clinical Hospital of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia (protocol No. 2e/9-19, dated April 2, 2019). All studies with the blood were carried out in accordance with the Helsinki Declaration of the World Medical Association of 2000 and the protocol of the Council of Europe Convention on Human Rights and Biomedicine of 1999. The blood samples were obtained with a voluntary informed consent of donors in the Blood Transfusion Department of the Russian Children’s Clinical Hospital of the Pirogov Russian National Research Medical University of the Ministry of Health of Russia.

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The author of this work declares that she has no conflicts of interest.

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Translated by A. Barkhash

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Vorobjeva, N.V. Involvement of Mitogen-Activated Protein Kinases p38 and ERK1/2, as well as Protein Kinase B Akt1/2, in the Formation of Neutrophil Extracellular Traps. Moscow Univ. Biol.Sci. Bull. 78, 219–224 (2023). https://doi.org/10.3103/S0096392523600722

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  • DOI: https://doi.org/10.3103/S0096392523600722

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