Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(3): 75-86


T.I. Gavrilenko1, N.А. Rizhkova1, O.M. Parkhomenko1, E.V. Dovgan1, N.V. Dovgan1, O.M. Pasichnichenko2, S.M. Babiy2

  1. State Institution NSC «The M. D. Strazhesko Institute of Cardiology National Academy of Medical Science of Ukraine»
  2. Taras Shevchenko National University of Kyiv, Ukraine


The review provides information on neutrophils, which are important effector cells of the innate immune response and form the first line of defence against infection. Issues of maturation and functional activity of cells are highlighted. The stages of the vital activity of neutrophils are shown – migration, chemotaxis, adhesion, oxygen explosion, absorption, degranulation, apoptosis. Special attention is paid to neutrophilic extracellular traps and the importance of myeloperoxidase. Today, these cells are increasingly viewed as a potential biomarker with specific treatments.

Keywords: neutrophils; immune response; immunocompetent cells.


  1. Pinegin BV, Mayansky AN. Neutrophils: structure and function. Immunology.2007;6:374-82 [Russian].
  2. Summers C, Rankin SM, Condliffe AM, Singh N, Peters AM, Chilvers ER. Neutrophil kinetics in health and disease. Trends Immunol. 2010;31:318-24. CrossRef PubMed PubMedCentral
  3. Rankin SM. The bone marrow: a site of neutrophil clearance. J Leukoc Biol. 2010;88:241-51. CrossRef PubMed
  4. Manz M G, Boettcher S. Emergency granulopoiesis. Nat Rev Immunol. 2014;14: 302-14. CrossRef PubMed
  5. Croce K, Libby P. Stirring the soup of innate immunity in the acute coronary syndromes. Eur Heart J. 2010 Jun;31(12):1430-2. CrossRef PubMed
  6. Hellberg L, Fuchs S, Gericke C, Sarkar A, Behnen M, Solbach W, Laskay T. Proinflammatory stimuli enchance phagocytosis of apoptotic cells by neutrophil granulocytes. Sci World J. 2011; 11:2230-6. CrossRef PubMed PubMedCentral
  7. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, Brohi K, Itagaki K, Hauser CJ. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104-7. CrossRef PubMed PubMedCentral
  8. Sadik C, Kim N, Luster A. Neutrophils cascading their way to inflammation. Trends Immunol. 2011 Oct; 32(10): 452-60. CrossRef PubMed PubMedCentral
  9. Eash KJ, Greenbaum AM, Gopalan PK, Link DC. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest. 2010;120: 2423-31 CrossRef PubMed PubMedCentral
  10. Németh T, Sperandio M, Mócsai A. Neutrophils as emerging therapeutic targets. Nat Rev Drug Disc. 2020;19:253-75 CrossRef PubMed
  11. Zeytun A, Chaudhary A, Pardington P, Cary R, Gupta G. Induction of cytokines and chemokines by Toll-like receptor signaling: strategies for control of inflammation. Crit Rev Immunol. 2010;30:53-67. CrossRef PubMed
  12. Chou RC, Kim ND, Sadik CD, Seung E, Lan Y, Byrne MH, Haribabu B, Iwakura Y, Luster AD. Lipid-Cytokinechemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity. 2010;33:266-78. CrossRef PubMed PubMedCentral
  13. Soehnlein O, Lindbom L, Weber C. Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood. 2009;114:4613-23. CrossRef PubMed
  14. Kovács M, Németh T, Jakus Z, Sitaru C, Simon E, Futosi K, Botz B, Helyes Z, Lowell CA, Mócsai A.The Src family kinases Hck, Fgr, and Lyn are critical for the generation of the in vivo inflammatory environment without a direct role in leukocyte recruitment. J Exp Med. 2014;211(10):1993-2011. CrossRef PubMed PubMedCentral
  15. Németh T, Mócsai A. Feedback amplification of neutrophil function. Trends Immunol. 2016;37;412-24. CrossRef PubMed
  16. McDonald B, Pittman K, Menezes GB, Hirota SA, Slaba I, CCM, PL, Muruve DA,Kubes P. Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science. 2010;330:362-6. CrossRef PubMed
  17. Dimasi D, Sun WY, Bonder CS. Neutrophil interactions with the vascular endothelium. Int Immun Pharmacol. 2013 Dec;17(4):1167-75. CrossRef PubMed
  18. ZhuYP, Padgett L, Dinh HQ, Marcovecchio P, Blatchley A, Wu R, Ehinger E, Kim C, Mikulski Z, Seumois G, Madriga A, Vijayanand P, Hedrick CC. Identification of an earlyunipotent neutrophil progenitor with pro-tumoral activity in mouse and human bonemarrow. Cell Rep. 2018;24:2329-41. CrossRef PubMed PubMedCentral
  19. Tsuda Y, Takahashi H, Kobayashi M, Hanafusa T, Herndon DN, Suzuki F. Three diferent neutrophil subsets exhibited in mice with diferent susceptibilities to infection by methicillin-resistant Staphylococcus aureus. Immunity. 2004;21:215-26. CrossRef PubMed
  20. Zhou G, Yu L, Fang L, Yang W, Yu T, Miao Y, et al. CD177(+) neutrophils as functionally activated neutrophils negatively regulate IBD. Gut. 2018; 67:1052-63. CrossRef PubMed
  21. Denny MF, Yalavarthi S, Zhao W, Thacker SG, Anderson M, Sandy AR, et al. A distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J Immunol. 2010; 184:3284-97. CrossRef PubMed PubMedCentral
  22. Lood C, Blanco LP, Purmalek MM, Carmona-Rivera C, De Ravin SS, Smith CK, et al. Neutrophil extracellular traps enriched in oxidized mitochondrial DNA are interferogenic and contribute to lupus-like disease. Nat Med. 2016; 22:146-53. CrossRef PubMed PubMedCentral
  23. Cascao R, Rosario H, Fonseca J. Neutrophils: warriors and commanders in immune mediated inflammatory diseases. Acta Reumatol. 2009;34(28);313-26.
  24. Rørvig S, Ostergaard O, Heegaard NH, Borregaard N. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: Correlation with transcriptome profiling of neutrophil precursors. J Leuk Biol. 2013; 94; 711-21. CrossRef PubMed
  25. AbaturovAE. Activated oxygen-containing metabolites - acomponent of the system of nonspecific protection of the respiratory tract. Health Shild. 2009;2(17):120-5.
  26. Brinkman V, Zychlinsky A. Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol. 2012;198(5):773-83. CrossRef PubMed PubMedCentral
  27. Klebanoff SJ. Myeloperoxidase: Friend and foe. J Leuc Biol. 2005;77:598-62. CrossRef PubMed
  28. Strzepa A, Pritchard K, Ditel B. Myeloperoxidase: a new player in autoimmunity. Cell Immunol. 2017; 317:1-8. CrossRef PubMed PubMedCentral
  29. Bergt C, Pennathur S, Fu X, Byun J, O'Brien K, McDonald TO, Singh P, AnantharamaiahGM, Chait A, Brunzell J, Geary RL, Oram JF. The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1-dependent cholesterol transport. Proc Natl Acad Sci USA. 2004 Aug 31;101(35):13032-7. CrossRef PubMed PubMedCentral
  30. Chen W, Liu N, Qi Y, Zhang Y, Deng Zh, J Yang J, Xie X. Changes of systemic and local myeloperoxidase and tumor necrosis factor-α in rats with myocardial injury induced by hindlimb ischemia-reperfusion. Nan Fang Yi Ke Da Xue Xue Bao. 2013 May;33(5):761-4.
  31. Chen W, Liu N, Qi Y, Zhang Y, Deng Zh, Yang J, Xie X. Changes of systemic and local myeloperoxidase and tumor necrosis factor-α in rats with myocardial injury induced by hind-limb ischemia-reperfusion. Nan Fang Yi Ke Da Xue Xue Bao. 2013 May;33(5):761-4.
  32. Nicholls SJ, Hazen SL. The role of myeloperoxidase in the pathogenesis of coronary artery disease. Jpn J Infect Dis. 2004;57;21-2.
  33. Soehnlein O. Multiple roles for neutrophils in atherosclerosis. Circ Res. 2012; 110:875-88. CrossRef PubMed
  34. Delporte C, Antwerpen P, Vanhamme L, Roumeguère T, Boudjeltia KZ. Low-density Lipoprotein modified by myeloperoxidase in inflammatory pathways and clinical studies. Mediat Inflamat. 2013:971579. CrossRef PubMed PubMedCentral
  35. Getz GS, Reardon CA. Myeloperoxidase-mediated dysfunctional high-density lipoprotein. Arterioscler Thromb Vascul Biol. 2014;34(4):695-6. CrossRef PubMed
  36. Zheng L, Nukuna B, Brennan ML, SunM, Goormastic M, Settle M, Schmitt D, Fu X, Thomson L, Fox PL, Ischiropoulos H, Smith JD, Kinter M, Hazen SL Apolipoprotein A-1 is a selective target for myeloperoxidase-catalyzed oxidation and functional impairment in subjects with cardiovascular disease. J Clin Invest. 2004;114:529-41. CrossRef
  37. Gavrilenko TI, Ryzhkova NA, Parkhomenko AN. Myeloperoxidase and its role in the development of coronary heart disease. Ukr Card Zh. 2014;4:119-26. [Russian].
  38. Korotina OL, Generalov II. Neutrophilic extracellular traps: mechanisms of formation, functions. Immunopath Allergol Infektol. 2012;4:23-32. [Russian].
  39. Fuchs TA, Abed U, Goosmann Ch, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol. 2007;176( 2):231-41. CrossRef PubMed PubMedCentral
  40. Papayannopoulos V, Metzler MD, Hakkim A, Zychlinsky A. Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. J Cell Biol. 2010; 191(3):677-91. CrossRef PubMed PubMedCentral
  41. Hoppenbrouwers T, Autar AS, Sultan AR, Abraham TE, Cappellen WA, Houtsmuller AB, Wamel WJ, Beusekom HM, Neck JW, Maat MP, In vitro induction of NETosis: Comprehensive live imaging comparison and systematic review. PLoS One. 2017;12: e0176472. CrossRef PubMed PubMedCentral
  42. Bonaventura A, Liberale L, Carbone F, Vecchié A, DiazCañestro C, Camici GG, Montecucco F, Dallegri F. The pathophysiological role of neutrophil extracellular traps in inflammatory diseases.Thromb Haemost. 2018 Jan;118(1):6-27. CrossRef PubMed
  43. Nakazawa D, Kumar S, Desai J, Anders H. Neutrophil extracellular traps in tissue pathology. Histol Histopathol. 2017; 32(3):203-13.
  44. Esmon, CT, Xu J, Lupu F. Innate immunity and coagulation. J Thromb Haemost. 2011;9:182-8. CrossRef PubMed PubMedCentral
  45. Fuchs TA, Brill A, Duerschmied D, Schatzberg D, Monestier M, Myers DD Jr. Extracellular DNA traps promote thrombosis. Proc Natl Acad Sci USA. 2010;107(36):15880-5. CrossRef PubMed PubMedCentral
  46. Saffarzadeh M, Juenemann C, Queisser MA, Lochnit G, Barreto G, Galuska SP, Lohmeyer J, Preissner KTJ. Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones. PLoS One. 2012; 7(2):e32366. CrossRef PubMed PubMedCentral
  47. Yang H, Biermann MH, Brauner JM, Liu Y, Zhao Y and Herrmann M. New insights into neutrophil extracellular traps: mechanisms of formation and role in inflammation. Front Immunol. 2016;7:302. CrossRef PubMed PubMedCentral
  48. Kevin R. Kasten, Jared T. Muenzer,Charles C. Caldwell neutrophils are significant producers of IL-10 during sepsis. Biochem Biophys Res Commun. 2010 Feb;393(26):28-31. CrossRef PubMed PubMedCentral
  49. Perobelli SM, Mercadante AC, Galvani RG, GoncalvesSilva T, Alves AP, Pereira-Neves A, Benchimol M, Nobrega A, Bonomo A. G-CSF-induced suppressor IL10+ neutrophils promote regulatory T cells that inhibit graftversus-host disease in a long-lasting and specific way. J Immunol. 2016;197:3725-34. CrossRef PubMed
  50. Tamassia N, Bianchetto-Aguilera F,Arruda-Silva F, Gardiman E, Gasperini S, Calzetti F, Cassatella MA. Cytokine production by human neutrophils: Revisiting the "dark side of the moon". Eur J Clin Invest. 2018 Nov;48, Suppl 2:e12952. CrossRef PubMed
  51. Marino F, Tozzi M, Schembri L. Ferraro S, Tarallo A, Scanzano A, Legnaro M, Castelli P, Cosentino M. Production of IL-8, VEGF and elastase by circulating and intraplaque neutrophils in patients with carotid atherosclerosis. PLoS One. 2015;10(4):e0124565. CrossRef PubMed PubMedCentral
  52. Kalyan Sh, Kabelitz D. When neutrophils meet T cells: Beginnings of a tumultuous relationship with under appreciated potential. Eur J Immunol. 2014; 44:627-33. CrossRef PubMed
  53. Mantovani, A, Cassatella, MA, Costantini C, Jaillon, S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011;11:519-31. CrossRef PubMed
  54. Mayadas TN, Cullere X, Lowell CA. The multifaceted functions of neutrophils. Annu Rev Pathol. 2014;9:181-218. CrossRef PubMed PubMedCentral
  55. Abdallah A, Egan CE, Butcher BA, Denkers EY. Mouse neutrophils are professional antigen-presenting cells programmed to instruct Th1 and Th17 T-cell differentiation. Int. Immunol. 2011; 23: 317-26. CrossRef PubMed PubMedCentral
  56. SchauerC,Janko C, Munoz LE, Zhao Y, Kienhöfer D, Frey B, Lell M, Manger B, Rech J, Naschberger E, Holmdahl R, Krenn V, Harrer T,Jeremic I, Bilyy R, Schett G, Hoffmann M, Herrmann M. Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines. Nat Med. 2014; 20: 511-7. CrossRef PubMed
  57. Fan J, FreyRS, MalikAB. TLR-4signaling induced TLR-2 expression in endothelial cells via neutrophil NADPH oxidase. J Clin Invest. 2003;112:1234-43. CrossRef PubMed PubMedCentral
  58. DarboussetR, ThomasGM, MezouarS, FrèreC, BonierR, MackmanN, RennéTh, Dignat-GeorgeF, DuboisCh, Panicot-DuboisL. Tissue factor-positive neutrophils bind to injured endothelial wall and initiate thrombus formation. Blood. 2012;120(10):2133-43. CrossRef PubMed
  59. Kimball AS, Obi AT, Diaz JA, Henke PK. The emerging role of NETs in venous thrombosis and immunothrombosis. Front Immunol. 2016;7:236. CrossRef PubMed PubMedCentral
  60. Furze RC, Rankin SM. Neutrophil mobilization and clearance in the bone marrow. Immunology. 2008 Nov;125(3):281-8. CrossRef PubMed PubMedCentral
  61. Wang J, Hossain M, Thanabalasuriar A, Gunzer M, Meininger C, Kubes P. Visualizing the function and fate of neutrophils in sterile injury and repair. Science. 2017;358:111-6. CrossRef PubMed
  62. Bratton DL, Henson PM. Neutrophil clearance: when the party is over, clean-up begins. Trends Immunol. 2011 Aug;32(8):350-7. CrossRef PubMed PubMedCentral
  63. Eghbalzadeh K, Georgi L, Louis T, Zhao H, Keser U, Weber C, Mollenhauer M, Conforti A, Wahlers T, PaunelGörgülü A. Compromised anti-inflammatory action of traps in PAD4-deficient mice contributes to aggravated acute inflammation after myocardial infarction. Front Immunol. 2019 Oct 1;10:2313. CrossRef PubMed PubMedCentral
  64. Stark MA, Huo Y, Burcin TL, Morris MA, Olson TS, Ley K. Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity. 2005; 22:285-94. CrossRef PubMed
  65. SchernbergA, BlanchardP, ChargariC, DeutschE. Neutrophils, a candidate biomarker and target for radiation therapy? Acta Oncol. 2017 Nov;56(11):1522-30. CrossRef PubMed
  66. Ryzhkova NO, Gavrilenko TI, Parkhomenko OM. Korvitin reduces the high level of myeloperoxidase in plasma of blood of patients with the acyte coronary syndrom. Fiziol Zh. 2016; 62(2):87-93. [Ukrainian]. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.