A modern view of the problem of NETosis-associated diseases

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Abstract

Neutrophilic granulocytes play an important role in the realization of innate immunity. In 2004, the phenomenon of netosis was discovered, accompanied by the release of neutrophil extracellular traps (NETs). Since then, a large number of studies have accumulated on their structure and function in pathological conditions. The purpose of this review is to highlight scientific achievements in the field of netosis research. The contribution of NETs to the pathogenesis of tissue alteration, inflammation, and thromboembolic complications was assessed. The main netosis-associated diseases in which the concentration of circulating NETs components such as extracellular DNA, myeloperoxidase, neutrophil elastase, and histones is increased have been identified. The basic information about the success of therapeutic drugs that destroy NETs structures is summarized. The diagnostic and prognostic value of NETs detection in the development of a wide range of diseases is shown. The presented material emphasizes the need to study NETs-associated diseases as a promising area for a doctor's practice.

About the authors

Yuliya E. Dobrokhotova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: pr.dobrohotova@mail.ru
ORCID iD: 0000-0003-2786-6181

MD, PhD, Professor

Russian Federation, Moscow

Ekaterina I. Borovkova

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: Katyanikitina@mail.ru
ORCID iD: 0000-0001-7140-262X
SPIN-code: 8897-8605

MD, PhD, Assistant Professor

Russian Federation, Moscow

Vladislava I. Klaushuk

Pirogov Russian National Research Medical University (Pirogov Medical University)

Email: doc.klaushuk@mail.ru
ORCID iD: 0009-0005-8515-6446
SPIN-code: 6479-8529

PhD Student

Russian Federation, Moscow

Natalia V. Nizyaeva

The Russian Scientific Center of Surgery Named after Academician B.V. Petrovsky

Email: niziaeva@gmail.com
ORCID iD: 0000-0001-5592-5690
SPIN-code: 9893-2630

MD, PhD

Russian Federation, Moscow

Ksenia A. Artemeva

The Russian Scientific Center of Surgery Named after Academician B.V. Petrovsky

Email: artemjeva_ksenia@mail.ru
ORCID iD: 0000-0002-1014-752X
SPIN-code: 2057-7745

MD, PhD, Leading Researcher

Russian Federation, Moscow

Alina N. Iakovleva

Pirogov Russian National Research Medical University (Pirogov Medical University)

Author for correspondence.
Email: A_L_I_N_A_0505@mail.ru
ORCID iD: 0009-0009-9235-7384

Resident

Russian Federation, Moscow

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2. Fig. 1. Implementation of the classical netosis pathway. Receptors on the surface of neutrophils perceive a wide range of signals that activate signaling pathways. Protein kinase C phosphorylates NADH oxidase subunits, leading to the formation of hydrogen peroxide and the synthesis of large amounts of ROS. An increase in calcium ion flux activates PAD4, followed by histone hypercitrullination. NE and MPO lead to chromatin decondensation. Gasdermin D forms nuclear pores through which chromatin fibers with serine proteases are released. In parallel, mitochondrial NETs may form

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