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Neutrophils as a Source of Factors Increasing Duration of the Inflammatory Phase of Wound Healing in Patients with Type 2 Diabetes Mellitus

  • E. V. MikhalchikEmail author
  • D. I. Maximov
  • E. M. Ostrovsky
  • A. V. Yaskevich
  • I. I. Vlasova
  • T. V. Vakhrusheva
  • L. Yu. Basyreva
  • A. A. Gusev
  • V. A. Kostevich
  • N. P. Gorbunov
  • A. V. Sokolov
  • O. M. Panasenko
  • S. A. Gusev
Article
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Abstract

Oxidative stress and neutrophil activation leading to an increase in myeloperoxidase (MPO), elastase and neutrophil extracellular trap (NET) levels in blood are considered as the pathogenic mechanisms responsible for the development of extremity damage in people with type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the relationship between factors, associated with neutrophil activation, and the duration of the initial phase of wound healing (the inflammatory phase) in T2DM patients. Patients were divided retrospectively into three groups depending on the severity of lower extent damage: group 1 (wound on toe) < group 2 (wound on foot) < group 3 (wound on lower leg). At admission to hospital, T2DM patients had significantly higher (р < 0.05) levels of blood glucose and glycated hemoglobin (groups 1−3), ESR (groups 1 and 3), blood neutrophil count (groups 2 and 3), plasma MPO concentration (groups 1−3) and blood NET concentration (group 3) and decreased levels of plasma thiols (groups 1−3) and erythrocyte glutathione peroxidase activity (groups 2 and 3) than in the control group (healthy volunteers). The length of hospital stay after surgery corresponded to the length of the inflammatory phase of the wound healing process and correlated with the number of blood neutrophils in patients before surgery (r = 0.72, p < 0.05). Leukocytic intoxication index depended on wound area (r = 0.59, р < 0.05), and it was significantly higher for groups 2 and 3 compared to the control group and group 1. The correlation found can be attributed to the increase in extracellular MPO and NETs due to the activation and degranulation of neutrophils and netosis. Thus, the duration of the inflammatory phase of wound healing depends on specific aspects of systemic inflammation increasing oxidative/halogenative stress and intoxication.

Keywords:

diabetes mellitus diabetic foot myeloperoxidase neutrophils neutrophil extracellular traps oxidative/halogenative stress 

Notes

REFERENCES

  1. 1.
    Dalla Paola, L., Carone, A., Vasilache, L., and Pattavina, M., Europ. Heart J., 2015, suppl. 17 (suppl. A), pp. A64–A68.  https://doi.org/10.1093/eurheartj/suv023
  2. 2.
    Girsh, A.O., Dolgikh, V.T., Lukach, V.N., Moroz, V.V., and Mal’kov, O.A., Obshchaya Reanimatologiya, 2005, vol. 1, no. 6, pp. 44–48.Google Scholar
  3. 3.
    Teuvov, A.A., Baziev, A.M., Lovpache, Z.N., Teunikova, I.S., and Chupodal, S.M., Biomed. Pharmacol. J., 2017, vol. 10, no. 4, pp. 1871–1878.  https://doi.org/10.13005/bpj/1306 CrossRefGoogle Scholar
  4. 4.
    Ceriello, A., Endocr. Pract., 2006, vol. 12, suppl. 1, pp. 60–62.CrossRefGoogle Scholar
  5. 5.
    Acharya, S.S., Padhy, R.K., and Rattan, R., J. Evol. Med. Dental Sci., 2012, vol. 1, no. 5, pp. 793–800.CrossRefGoogle Scholar
  6. 6.
    Pavelkin, A.G. and Belyaev, A.N., Vest. Novykh Med. Tekhnol., 2013, vol. 20, no. 3, pp. 26–32.Google Scholar
  7. 7.
    Ullah, A., Khan, A., and Khan, I., Saudi Pharmaceutical J., 2016, vol. 24, pp. 547–553.CrossRefGoogle Scholar
  8. 8.
    Panasenko, O.M., Gorudko, I.V., and Sokolov, A.V., Uspekhi Biologicheskoi Khimii, 2013, vol. 53, pp. 195–244.Google Scholar
  9. 9.
    Tukin, V.N., Uspekhi Sovremennogo Estestvoznaniya, 2007, vol. 12, no. 1, pp. 62–63.Google Scholar
  10. 10.
    Kovalchuk, L.V., Potemkin, V.V., Baldina, T.N., and Barbin, P.B., Vestnik Eksper. Klin. Khirurg., 2011, vol. 4, no. 1, pp. 85–89.Google Scholar
  11. 11.
    Ostrovskii, V.K. and Svitich, Yu.N., Vestnik Khirurgii imeni I.I. Grekova, 1983, vol. 131, no. 11, pp. 21–24.Google Scholar
  12. 12.
    Wong, S.L., Demers, M., Martinod, K., Gallant, M., Yanming, W., Goldfine, A.B., Kahn, C.R., and Wagner, D.D., Nat. Med., 2015, vol. 21, no. 7, pp. 815–819.  https://doi.org/10.1038/nm.3887 CrossRefGoogle Scholar
  13. 13.
    Fadini, G.P., Menegazzo, L., Rigato, M., Scattoloi-ni, V., Poncina, N., Bruttocao, A., Ciciliot, S., Mammano, F., Ciubotaru, C.D., Brocco, E., Marescotti, M.C., Cappellari, R., Arrigoni, G., Millioni, R., Vigilii de Kreutzenberg, S., Albiero, M., and Avogaro, A., Diabetes, 2016, vol. 65, no. 4, pp. 1061–1071.  https://doi.org/10.2337/db15-0863 CrossRefGoogle Scholar
  14. 14.
    Basyreva, L., Brodsky, I., Gusev, A., Zhapparova, O., Mikhalchik, E., Gusev, S., Shor, D., Dahan, S., Blank, M., and Shoenfeld, Y., Human Antibodies, 2015/2016, vol. 24, nos. 3–4, pp. 39–44.  https://doi.org/10.3233/HAB-160293 CrossRefGoogle Scholar
  15. 15.
    Hu, M.-L., Methods Enzymol., 1994, vol. 233, pp. 380–385.CrossRefGoogle Scholar
  16. 16.
    Gorudko, I.V., Cherkalina, O.S., Sokolov, A.V., Pulina, M.O., Zakharova, E.T., Vasil’yev V.B., Cherenkevich, S.N., and Panasenko, O.M., Bioorgan. Khim., 2009, vol. 35, no. 5, pp. 629–639.Google Scholar
  17. 17.
    Gavrilova, A.N. and Khmara, N.F., Lab. Delo, 1986, no. 12, pp. 721–724.Google Scholar
  18. 18.
    Aruoma, O.I. and Halliwell, B., Biochem. J., 1987, vol. 248, pp. 973–976.CrossRefGoogle Scholar
  19. 19.
    Jandrić-Balen, M., Božikov, V., Božikov, J., Metelko, Ž., Jandrić, I., and Romić, Ž., Diabetologia Croatica, 2005, vol. 33, no. 4, pp. 131–135.Google Scholar
  20. 20.
    Ghosal, K., Das, S., Aich, K., Goswami, S., Chowdhury, S., and Bhattacharyya, M., Clin. Chim. Acta, 2016, vol. 458, pp. 144–153.  https://doi.org/10.1016/j.cca.2016.05.006 CrossRefGoogle Scholar
  21. 21.
    Jorch, S.K. and Kubes, P., Nature Medicine, 2017, vol. 23, no. 3, pp. 279–287.  https://doi.org/10.1038/nm.4294 CrossRefGoogle Scholar
  22. 22.
    Vita, J.A., Brennan, M.-L., Gocke, N., Mann, S.A., Goormastic, M., Shishebor, M.H., Penn, M.S., Keaney, J.F., and Hazen, S.L., Circulation, 2004, vol. 110, pp. 1134–1139.CrossRefGoogle Scholar
  23. 23.
    Goutos, I., Nicholas, R.S., Pandya, A.A., and Ghosh, S.J., Int. J. Burn Trauma, 2015, vol. 5, no. 1, pp. 1–12.Google Scholar
  24. 24.
    Wlaschek, M. and Scharffetter-Kochanek, K., Wound. Repair Regen., 2005, vol. 13, no. 5, pp. 452–461.  https://doi.org/10.1111/j.1067-1927.2005.00065.x CrossRefGoogle Scholar
  25. 25.
    Berezin, A., Biomed. Res. Ther., 2016, vol. 3, no. 5, pp. 618–624.  https://doi.org/10.7603/s40730-016-0021-9 Google Scholar
  26. 26.
    Menegazzo, L., Scattolini, V., Cappellari, R., Bonora, B.M., Albiero, M., Bortolozzi, M., Romanato, F., Ceolotto, G., Vigili de Kteutzeberg, S., Avogaro, A., and Fadini, G.P., Acta Diabetologica, 2018,  https://doi.org/10.1007/s00592-018-1129-8

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • E. V. Mikhalchik
    • 1
    Email author
  • D. I. Maximov
    • 1
  • E. M. Ostrovsky
    • 1
  • A. V. Yaskevich
    • 1
  • I. I. Vlasova
    • 1
  • T. V. Vakhrusheva
    • 1
  • L. Yu. Basyreva
    • 1
  • A. A. Gusev
    • 1
  • V. A. Kostevich
    • 1
    • 2
  • N. P. Gorbunov
    • 1
    • 3
  • A. V. Sokolov
    • 1
    • 2
  • O. M. Panasenko
    • 1
  • S. A. Gusev
    • 1
  1. 1.Federal Research and Clinical Center of Physical-Chemical MedicineMoscowRussia
  2. 2.Institute of Experimental MedicineSaint-PetersburgRussia
  3. 3.State Research Institute of Highly Pure BiopreparationsSaint-PetersburgRussia

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