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Effect of Xenon on Proinflammatory Activation and Apoptosis of Human Neutrophils Under Ex Vivo Conditions

https://doi.org/10.23934/2223-9022-2021-10-3-511-520

Abstract

Background. The syndrome of systemic inflammatory response, which underlies the damaging effect of factors of infectious and non-infectious genesis, may cause multiple organ failure. The degree of its severity is determined, among other things, by the activation of neutrophils. The paper highlights new mechanisms of the anti-inflammatory action of the inhalation anesthetic xenon, mediated by a decrease in the ability of neutrophils to pro-inflammatory response.
Aim of study. To evaluate the effect of xenon on the activation of human neutrophils under ex vivo conditions.
Material AND methods. We studied the effect of xenon inhalation on reduction of the ability of neutrophils to be activated proinflammatory by reduced expression of adhesion molecules CD11b and CD66b on the surface of neutrophils and on the phosphorylation of proinflammatory kinases: ERK 1/2 and kinase — p38 in neutrophils of healthy volunteers.
Results. The use of xenon at a dose of 30 vol. % within 60 minutes in healthy volunteers statistically significantly reduces the ability of neutrophils to proinflammatory activation. The addition of lipopolysaccharide (LPS) to the incubation medium of neutrophils causes their pronounced activation, statistically significantly increasing the phosphorylation of key proinflammatory neutrophil kinases ERK1/2 and kinase p38. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on LPS-stimulated neutrophils, decreasing their activation by inhibiting pro-inflammatory kinase ERK1/2 and pro-inflammatory MAP kinase p38.
Conclusion. The actual study, performed on isolated neutrophils from volunteers who underwent xenon inhalation, revealed the anti-inflammatory properties of the inert gas xenon, which, in our opinion, may have a direct relationship to the identification of the mechanism of its neuroprotective properties. Thus, the research results available today suggest that xenon has a pronounced pleiotropic mechanism of brain protection. This is a partial blockade of NMDA receptors, and phosphorylation of the enzyme glycogen synthase-3β, and limitation of the inflammatory activation of neutrophils.
Findings. Inhalation of xenon in volunteers (30% within 60 minutes) has a pronounced anti-inflammatory effect on neutrophils stimulated by lipopolysaccharides, decreasing their activation by inhibiting proinflammatory ERK 1/2 kinase and proinflammatory MAP kinase p38, as well as reducing the expression of markers of activation and degranulation CD11b and CD66b on the surface of neutrophils. Stimulation by lipopolysaccharides statistically significantly reduces spontaneous apoptosis of neutrophils, while xenon increases the ability of neutrophils to apoptosis, which is likely to contribute to the resolution of inflammation.

About the Authors

O. A. Grebenchikov
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation
Russian Federation

Doctor of Medical Sciences, Chief Researcher of the Laboratory for Organ Protection in Critical Conditions

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 



A. K. Shabanov
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation; N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Health Department
Russian Federation

Doctor of Medical Sciences, Chief Researcher of the Laboratory of Clinical Pathophysiology In Critical Conditions;  Deputy Chief Physicians for Anesthesiology and Resuscitation

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 

 3 B. Sukharevskaya Sq., Moscow 129090, Russian Federation 



L. L. Nikolayev
Russian Medical Academy of Continuing Professional Education
Russian Federation

Associate Professor of the Department of Anesthesiology and Resuscitation

2/1, building 1 Barrikadnaya St., Moscow 125993, Russian Federation 



A. I. Shpichko
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation
Russian Federation

Candidate of Medical Sciences, Senior Researcher of the Laboratory for Organ Protection in Critical Conditions

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 



I. V. Bratishchev
N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Health Department
Russian Federation

 Anesthesiologist-resuscitator, Lecturer of the Educational Department 

 3 B. Sukharevskaya Sq., Moscow 129090, Russian Federation 



L. Yu. Marchenko
State Scientific Center of the Russian Federation Institute of Biomedical Issues of the Russian Academy of Sciences
Russian Federation

 Junior Researcher of the State Scientific Center  

76A, p. 4 Horoshevskoe Sh., Moscow 123007, Russian Federation 



Sh. Zh. Khusainov
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation;N.V. Sklifosovsky Research Institute for Emergency Medicine of the Moscow Health Department
Russian Federation

Anesthesiologist-resuscitator, postgraduate student 

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 

 3 B. Sukharevskaya Sq., Moscow 129090, Russian Federation 



R. A. Cherpakov
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation
Russian Federation

Researcher of the Laboratory for Organ Protection in Critical Conditions

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 



N. P. Shpichko
Federal Scientific and Clinical Center of Resuscitation and Rehabilitation; Peoples’ Friendship University of Russia
Russian Federation

 Researcher at the Laboratory of Motor Rehabilitation, Swallowing and Speech Recovery, Assistant of the Department of Anesthesiology,  Resuscitation and Intensive Therapy 

 25 building 2 Petrovka St., Moscow 107031, Russian Federation 

6 Miklukho-Maklaya St., Moscow 117198, Russian Federation



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Review

For citations:


Grebenchikov O.A., Shabanov A.K., Nikolayev L.L., Shpichko A.I., Bratishchev I.V., Marchenko L.Yu., Khusainov Sh.Zh., Cherpakov R.A., Shpichko N.P. Effect of Xenon on Proinflammatory Activation and Apoptosis of Human Neutrophils Under Ex Vivo Conditions. Russian Sklifosovsky Journal "Emergency Medical Care". 2021;10(3):511-520. https://doi.org/10.23934/2223-9022-2021-10-3-511-520

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ISSN 2223-9022 (Print)
ISSN 2541-8017 (Online)