The severity of netosis in patients with neonatal sepsis
https://doi.org/10.21508/1027-4065-2020-65-5-164-168
Abstract
Objective. To evaluate the severity of spontaneous netosis in peripheral blood in neonatal children with sepsis.
Characteristics of children and research methods. The researchers have studied the severity of spontaneous netosis in 12 neonates with sepsis who were hospitalized in the neonatal intensive care unit of the City Children’s Hospital No.1 in Kazan. The diagnose was based on a systemic inflammatory response syndrome, an increase in the concentration of C-reactive protein in the blood of more than 1 mg/dL, the presence of one or more foci of infection, the development of organ dysfunction, and the presence of a microorganism in venous blood.
Results. It was found that the initial period of neonatal sepsis proceeds against the background of activation of netosis, which was manifested by neutrophil extracellular traps in the peripheral blood. Their quantity and percentage was significantly higher compared to the indicators of the control group (p=0.02 and p=0.0007 accordingly). The highest levels of neutrophils in the state of netosis (67% and 70%) were found in 2 neonates with septic shock and leukopenia (2.7·109/L and 2.8·109/L, respectively). Only one neonate with septic shock developed absolute neutropenia (less than 2•109/L) and leukopenia (less than 5·109 / L). Thrombocytopenia was noted in 5 of 12 neonates with sepsis, which was less than 100•109/L in every fourth child. At the same time, there were no clinical cases of hemorrhagic syndrome and blood clotting disorders.
Conclusion. The formation of neutrophilic extracellular traps is one of the most important mechanisms of anti-infective protection aimed at arresting the inflammatory process and clearing the internal media of the body.
About the Authors
Kh. S. KhaertynovRussian Federation
V. A. Anokhin
Russian Federation
G. V. Galina
Russian Federation
S. V. Boychuk
Russian Federation
N. V. Dontsova
Russian Federation
Tatarstan, Kazan
References
1. Verma P., Berwal P.K., Nagaraj N. Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Int J Contemp Pediatr 2015; 2 (3): 176-180. DOI: 10.18203/2349-3291.ijcp20150523
2. Camacho-Gonzales A., Spearman P.W., Stoll B.J. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013; 60: 367-389. DOI: 10.1016/j.pcl.2012.12.003
3. Bryce J., Black R.E., Walker N., Bhutta Z.A., Lawn J.E., Ste-ketee R.W. Can the world afford to save the lives of 6 million children each year? Lancet 2005; 365: 2193-2200.
4. Олс Р, Едер М. Гематология, иммунология и инфекционные болезни. М.: 2013; 408. [Ols R., Eder M. Hematology, immunology and infectious diseases. M.: 2013; 408. (in Russ.)]
5. Melvan J.N., Bagby G.J., Welsh D.A., Nelson S, ZhangP. Neonatal sepsis and neutrophil insufficiencies. Int Rev Immunol 2010; 29: 315-348. DOI: 10.3109/08830181003792803
6. Cooper P.R., Palmer L.J., Chapple I.L.C. Neutrophil extracellular traps as a new paradigm in innate immunity: friend or foe? Periodontol 2000; 63(1): 165-197. DOI: 10.1111/prd.12025
7. McDonald B., Urrutia R, Yipp B.G., Jenne C.N., Kubes P. Intravascular neutrophil extracellular traps capture bacteria from the bloodstream during sepsis. Cell Host Microbe 2012; 12: 324-33. DOI: 10.1016/j.chom.2012.06.011
8. Nathan C. Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 2006; 6: 173-182. DOI: 10.1038/nri1785
9. Iba T., Hashiguchi N., Nagaoka I., Tabe Y., Muray M. Neutrophil cell death in response to infection and its relation to coagulation. J Intens Care 2013; 1: 13. DOI: 10.1186/2052-0492-1-13.
10. Martinelli S., Urosevic M., Daryadel A., Oberholzer P.A., Baumann C., Fey M.F. et al. Induction of genes mediating interferon-dependent extracellular trap formation during neutrophil differentiation. J Biol Chem 2004; 279: 44123-44132. DOI: 10.1074/jbc.M405883200
11. Nguyen D.N., Stensballe A., Lai J.C., Jiang P., Brunse A., Li Y. et al. Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants. Innate Immun 2017; 23: 524-36. DOI: 10.1177/1753425917719995
12. Vincent D., Klinke M., Eschenburg G., Trochimiuk M., Appl B., Tiemann B. et al. NEC is likely a NETs dependent process and markers of NETosis are predictive of NEC in mice and humans. Sci Rep 2018; 8: 12612. DOI: 10.1038/s41598-018-31087-0
13. Lipp Р, Ruhnau J., Lange A., Vogelgesang A., Dressel A., Heckmann M. Less Neutrophil Extracellular Trap Formation in Term Newborns than in Adults. Neonatology 2017; 111: 182-188. DOI: 10.1159/000452615
14. Brinkmann V., Zychlinsky A. Beneficial suicide: why neutrophils die to, make NETs. Nature Rev 2007; 5: 577-582. DOI: 10.1038/nrmicro1710.
15. Lipiaska-Gediga M. Neutrophils, NETs, NETosis - old or new factors in sepsis and septic shock? Anaesthesiol Intens Therapy 2017; 49(3): 235-240. DOI: 10.5603/AIT.2017.0041.
16. Clark S.R., Ma A.C., Tavener S.A., McDonald B., Goodarzi Z., Kelly M.M. et al. Platelet TLR4 activates neutrophil extracellular traps to ensnare bacteria in septic blood. Nat Med 2007; 13: 463-469. DOI: 10.1038/nm1565
17. Tanaka K., Koike Y., Shimura T., Okigami M., Ide S., Toiya-ma Y. et al. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model. PLoS ONE 2014; 9: e111888. DOI: 10.1371/journal.pone.0111888
18. Angus D.C., van der Poll T. Severe sepsis and septic shock. Engl J Med 2014: 369 (9): 840-851. DOI: 10.1056/NEJMra1208623.
Review
For citations:
Khaertynov Kh.S., Anokhin V.A., Galina G.V., Boychuk S.V., Dontsova N.V. The severity of netosis in patients with neonatal sepsis. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2020;65(5):164-168. (In Russ.) https://doi.org/10.21508/1027-4065-2020-65-5-164-168