Systemic and local effective function of neutrophilic granulocytes associated with transformation of the phenotype of their functionally significant subset in children with small purulent infection

Cover Page

Abstract


Defects in the functioning of neutrophilic granulocytes (NG) are accompanied by various purulent-inflammatory diseases that have a persistent-relapsing course. The bactericidal activity of NG, the processes of intracellular and extracellular killing of bacteria, is directly dependent on their phenotypic features: the expression level of functionally significant membrane receptors CD64, CD16, CD32, CD11b triggering effector processes. It was shown that there are subsets of NG with different phenotypic characteristics and the course and outcome of infectious and inflammatory diseases directly depends on their usefulness. Despite the large amount of accumulated information, the question of the transformation of NG subpopulations phenotype during NG response formation in children with local purulent processes of soft tissues - a small purulent infection (SPI) remains poorly understood. Purpose: to evaluate the local and systemic effector function of neutrophilic granulocytes (phagocytosis, NET formation) with clarification of the phenotype of functionally significant CD64-CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and CD64-CD16+CD32-CD11b+ NG subpopulations in peripheral blood (PB) in children with SPI. Materials and methods. We evaluated the phagocytic function of NG in 60 PB samples of children 5-9 years old, on the 2-3rd day of acute purulent process, before surgery, in smears - prints taken from the local focus of purulent inflammation and 17 PB samples of conditionally healthy children. Also the ability to form NET was additionally determined in smears-prints in children with SPI. In parallel, in PB we evaluated:% NG simultaneously carrying CD64, CD16, CD32, CD11b receptors and their expression density (MFI) by flow cytometry (CYTOMICS FC500, Beckman Coulter, USA). Statistical data processing was performed in the Microsoft Exel 2016 and Stat Plus 2010 software packages. Nonparametric criteria were used: median (Me) and interquartile range (Q1; Q3), Mann-Whitney U-test and Wilcoxon test. Results . We found a significant increase in the content of the NG subpopulation with a negatively transformed phenotype CD64-CD16+CD32-CD11b+ with defects in the expression of CD64 and CD32 receptors, which is the cause of inadequate inclusion of NG in inflammatory processes, disruption of phagocytic activity at the systemic and local levels and the occurrence of SPI in children. The formation of NET in the first stage is necessary to supplement the effector function of NG in order to compensate for disorders of phagocytosis.


About the authors

G. A Chudilova

Kuban State Medical University

Author for correspondence.
Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

I. V Nesterova

Kuban State Medical University; Peoples’ Friendship University of Russia (RUDN University)

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation; Moscow, Russian Federation

T. V Rusinova

Kuban State Medical University

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

S. V Kovaleva

Kuban State Medical University

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

V. N Pavlenko

Kuban State Medical University

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

V. A Tarakanov

Kuban State Medical University

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

N. K Barova

Kuban State Medical University

Email: chudilova2015@yandex.ru
Krasnodar, Russian Federation

References

  1. Sepiashvili R.I. Physiology of the immune system. Moscow: Medicine — Health, 2019. 360 p. (In Russ.)
  2. Dolgushin I.I. Neutrophil granulocytes: new faces of old acquaintances. Bulletin of Siberian Medicine. 2019;18(1): 30—7. (In Russ.)
  3. Yang F., Feng C., Zhang X., Lu J., Zhao Y. The diverse biological functions of neutrophils, beyond the defense against infections. Inflammation. 2017;40: 311—23.
  4. Mantovani А., Cassatella M.C., Costantini C., Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nature Reviews Immunology. 2011;11: 519—31.
  5. Yang H., Biermann M.H., Brauner J.M., Liu Y., Zhao Y., Herrmann M. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation. Front. Immunol. 2016; 7:302.
  6. Nesterova I.V., Kolesnikova N.V., Chudilova G.A., Lomtatidze L.V., Kovaleva S.V., Evglevsky A.A., Nguyen T.Z.L. A new look at neutrophilic granulocytes: rethinking old dogmas. (Part 2). Infection and immunity. 2017; 7(3): 219—30. (In Russ.)
  7. Nesterova I.V., Chudilova G.A., Kovaleva S.V., Tarakanov V.A., Lomtatidze L.V., Kolesnikova N.V., Rusinova T.V., Yevglevsky A.A. Neutrophilic granulocytes: reflection in the mirror of modern ideas. Capricorn Publishing, UK, USA, Moscow, 2018. 338 p. (In Russ.)
  8. Beyrau M., Bodkin J.V., Nourshargh S. Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity. Open Biol. 2012;2:120—34.
  9. Scapini P., Marini O., Tecchio C., Cassatella M.A. Human neutrophils in the saga of cellular heterogeneity: insights and open questions. Immunol. Rev. 2016; 273(1):48—60.
  10. Garley M., Jabłońska E. Heterogeneity among neutrophils. Arch. Immunol. Ther. Exp. (Warsz). 2018; 66(1):21—30.
  11. Cortjens B., Ingelse S.A., Calis J.C., Vlaar A.P., Koenderman L., Bem R.A., van Woensel J.B. Neutrophil subset responses in infants with severe viral respiratory infection. Clinical immunology. 2017; 176: 100—106.
  12. Silvestre-Roig C., Hidalgo A., Soehnlein O. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood. 2016; 127: 2173—81.
  13. Bournazos S., Wang T., Ravetch J.V. The role and function of Fcγ receptors on myeloid cells. Microbiology spectrum. 2016; 4(6):10.
  14. Yin W. P., Li J.B., Zheng X.F., An L., Shao H., Li C.S. Effect of neutrophil CD64 for diagnosing sepsis in emergency department. World journal of emergency medicine. 2020;11(2): 79—86.
  15. El-Madbouly A.A., El Sehemawy A.A., Eldesoky N.A., Abd Elgalil H.M., Ahmed A.M. Utility of presepsin, soluble triggering receptor expressed on myeloid cells-1, and neutrophil CD64 for early detection of neonatal sepsis. Infect. Drug Resist. 2019;12: 311—19.
  16. Metelitsa L.S., Gillies S.D., Super M., Shimada H., Reynolds C.P., Seeger R.C. Antidisialogangliosid/granulocyte macrophage — colony-stimulating factor fusion protein facilitates neutrophil antibody-dependent cellular cytotoxicity and depends on FcγRII (CD32) and Mac-1 (CD11b/CD18) for enhanced effector cell adhesion and azurophil granule exocytosis. Blood. 2002; 99 (11): 4166—73
  17. Lau D., Mollnau H., Eiserich J.P., Freeman B.A., Daiber A., Gehling U.M., Brümmer J., Rudolph V., Münzel T., Heitzer T., Meinertz T., Baldus S. Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins. Proc. Natl. Acad. Sci. USA. 2005; 102(2): 431—6.
  18. Kiseleva E.P. New ideas on anti-infectious immunity. Infection and immunity. 2011;1(1): 9—14. (In Russ.)
  19. Elghetany M.T. Surface antigen changes during normal neutrophilic development: a critical review. Blood Cells Mol. Dis. 2002; 28(2): 260—74.
  20. Fortunati E., Kazemier K.M., Grutters J.C., Koenderman L., Van Den Bosch V.J. Human neutrophils switch to an activated phenotype after homing to the lung irrespective of inflammatory disease. Clin. Exp. Immunol. 2009; 155:559—66.

Statistics

Views

Abstract - 144

PDF (Russian) - 101

Cited-By


PlumX

Dimensions


Copyright (c) 2020 Chudilova G.A., Nesterova I.V., Rusinova T.V., Kovaleva S.V., Pavlenko V.N., Tarakanov V.A., Barova N.K.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies