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Features of extracellular trap formation in response to neutrophil leukocyte stimulation by thrombin in patients with diabetes mellitus and various types of diabetic foot damage

[Internal diseases]
Inna Viktorovna Druk; Dmitry Georgyevich Novikov; Alexander Nikolaevich Zolotov; Nikolay Aleksandrovich Kirichenko; Elizaveta Alexandrovna Kirch; Albina Yuryevna Savochkina; Vladimir Vladimirovich Khodus; Elena Albertovna Sorokina;

We determined the ability of extracellular traps to be formed by blood cells in fractions of mononuclear cells and granulocytes in patients with type 1 and type 2 diabetes mellitus complicated by diabetic foot syndrome without (n=10) and with Charcot neuro osteoarthropathy (n=8). The mononuclear cell fraction of patients contained 15–30 % of low density neutrophils (LDNs), whereas their proportion in the control group (n=12) was minimal. Spontaneous and thrombin stimulated formation of filamentous extracellular traps was most pronounced in patients with neuro-osteoarthropathy. Furthermore, this group exhibited a significant increase in the levels of interleukin-8 (4.4-fold) and citrullinated histone H3 (5.7-fold) compared to the control group. The obtained data indicate a probable role of LDN-mediated inflammation in the pathogenesis of Charcot neuro-osteoarthropathy.

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References:
1. Zhu Y., Xia X., He Q., Xiao Q. A., Wang D. [et al.]. Diabetes-associated neutrophil NETosis: pathogenesis and interventional target of diabetic complications. Front. Endocrinol. (Lausanne). 2023;14:1202463. https://doi.org/10.3389/fendo.2023.1202463
2. Volmer-Thole M., Lobmann R. Neuropathy and Diabetic Foot Syndrome. International J. Mol. Sci. 2016;17(6):917. https://doi.org/10.3390/ijms17060917
3. Njeim R., Azar W. S., Fares A. H., Azar S. T., Kfoury Kassouf H., Eid A. A. NETosis contributes to the pathogenesis of diabetes and its complications. J. Mol. Endocrinol. 2020;65(4):R65-R76. https://doi.org/10.1530/JME-20-0128
4. Dumont B. L., Neagoe P.-E., Charles E., Villeneuve L., Tardif J.-C. [et al.]. Low-Density Neutrophils Contribute to Subclinical Inflammation in Patients with Type 2 Diabetes. Int. J. Molecular Sci. 2024;25(3):1674. https://doi.org/10.3390/ijms25031674
5. Fu Y., Wen Z., Fan J. Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation. Mol. Med. 2025;31:133. https://doi.org/10.1186/s10020-025-01053-1
6. Hong C. W. Current Understanding in Neutrophil Differentiation and Heterogeneity. Immune Netw. 2017;17(5):298-306. https://doi.org/10.4110/in.2017.17.5.298
7. Wong S. L., Demers M., Martinod K., Gallant M., Wang Y. [et al.]. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat. Med. 2015;21(7):815-819. https://doi.org/10.1038/nm.3887
8. Denny M. F., Yalavarthi S., Zhao W., Thacker S. G., Anderson M. [et al.]. Distinct subset of proinflammatory neutrophils isolated from patients with systemic lupus erythematosus induces vascular damage and synthesizes type I IFNs. J. Immunol. 2010;184(6):3284-3297. https://doi.org/10.4049/jimmunol.0902199
9. Marini O., Costa S., Bevilacqua D., Calzetti F., Tamassia N. [et al.]. Mature CD10+ and immature CD10– neutrophils present in G-CSF-treated donors display opposite effects on T cells. Blood. 2017;129(10):1343-1356. https://doi.org/10.1182/blood-2016-04-713206
10. Sagiv J. Y., Michaeli J., Assi S., Mishalian I., Kisos H. [et al.]. Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer. Cell. Rep. 2015;10(4):562-573. https://doi.org/10.1016/j.celrep.2014.12.039
11. Ibrahim N., Knöbl V., Hayden H., Bauer W. M., Worel N. [et al.]. Human monocyte subsets differ in their capacity to form extracellular traps. Cell. Death Discovery. 2024;10(1):281. https://doi.org/10.1038/s41420-024-02034-y
12. de Bont C. M., Boelens W. C., Pruijn G. J. M. NETosis, complement, and coagulation: a triangular relationship. Cell. Mol. Immunol. 2019;16(1):19-27. https://doi.org/10.1038/s41423-018-0024-0
13. Zhu Y., Xia X., He Q., Xiao Q.-A., Wang D. [et al.]. Genetic Polymorphisms of PADI4 and Their Clinical Implications in Diabetic Patients Undergoing Orthopedic or Traumatological Surgery. Diagnostics (Basel). 2024;14(6):673. https://doi.org/10.3390/diagnostics14060673
14. Yang S., Gu Z., Lu C., Zhang T., Guo X. [et al.]. Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients with Diabetic Foot Ulcers Treated in a Multidisciplinary Setting. Adv. Wound. Care (New Rochelle). 2020;9(1):16-27. https://doi.org/10.1089/wound.2019.0943
15. Tilley D. O., Abuabed U., Zimny Arndt U., Schmid M., Florian S. [et al.]. Histone H3 clipping is a novel signature of human neutrophil extracellular traps. Elife. 2022;11:e68283. https://doi.org/10.7554/eLife.68283
16. Novikov D. G., Zolotov A. N., Indutny A. V., Mordyk A. V., Kirichenko N. A. [et al.]. NETs production and citrullinated histone H3 level in children with tuberculosis. Byulleten sibirskoj mediciny. – Bulletin of Siberian Medicine. 2024;23(4):95-104. (In Russ.). https://doi.org/10.20538/1682-0363-2024-4-95-104
17. Karasu E., Halbgebauer R., Schütte L., Greven J., Bläsius F. M. [et al.]. A conformational change of C-reactive protein drives neutrophil extracellular trap formation in inflammation. BMC Biol. 2025;23(1):4. https://doi.org/10.1186/s12915-024-02093-8
18. Vulesevic B., Lavoie S. S., Neagoe P. E., Dumas Е., Räkel А. [et al.]. CRP induces NETosis in heart failure patients with or without diabetes. Immunohorizons. 2019;3(8):378-388. https://doi.org/10.4049/immunohorizons.1900026
19. Teijeira A., Garasa S., Ochoa M. D. C., Cirella A., Olivera I. [et al.]. Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils. Eur. J. Immunol. 2021;51(9):2274-2280. https://doi.org/10.1002/eji.202049029
20. Marcos-Jubilar M., Lecumberri R., Páramo J. A. Immunothrombosis: Molecular Aspects and New Therapeutic Perspectives. J. Clin. Med. 2023;12(4):1399. https://doi.org/10.3390/jcm12041399
21. Lim C. H., Adav S. S., Sze S. K., Choong Y. K., Saravanan R., Schmidtchen A. Thrombin and Plasmin Alter the Proteome of Neutrophil Extracellular Traps. Front. Immunol. 2018;9:1554. https://doi.org/10.3389/fimmu.2018.01554
22. Yousefi S., Simon H. U. NETosis – Does It Really Represent Nature’s «Suicide Bomber»? Front. Immunol. 2016;7:328. https://doi.org/10.3389/fimmu.2016.00328

Keywords: diabetes mellitus, diabetic foot syndrome, neuro-osteoarthropathy, low-density neutrophils, netosis, neutrophil extracellular traps, citrullinated histone H3, interleukin-8, C-reactive protein


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Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy