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

Mikhalchik, Elena V.; Maximov, D I; Ostrovsky, E M; Yaskevich, Andrey Vladimirovich; Vlasova, Irina I.; Вахрушева, Т. В.; Basyreva, L. Yu.; Gusev, Alexander; Kostevich, Valeria A.; Горбунов, Н. П.; Sokolov, A. V.; Панасенко, О. М.; Гусев, С. А.

doi:10.1134/s1990750819010098

Cited by 3 publications

(2 citation statements)

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“…T2DM complicated by purulent necrotizing ulcers on the lower limbs is characterized by a long progressive course, which is associated with the development of vascular pathology and chronic nonhealing wounds with chronic inflammation. We have previously shown that the blood of mostly severe patients has high concentrations of NETs [12,13].…”

Section: Discussionmentioning

confidence: 98%

“…It has been indeed repeatedly observed that excessive NET formation is linked to the development of autoimmune, cardiovascular, and endocrine diseases, including diabetes mellitus. In particular, our data have shown that in type 2 diabetes mellitus (T2DM) patients with purulent necrotizing lesions of the lower extremities, a more severe clinical course is associated with a higher blood NET level [12,13]. NETosis promotes microthrombosis as well as causes delayed wound healing [9,14,15], which could have a negative effect on the healing process in T2DM patients.…”

Section: Introductionmentioning

confidence: 95%

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Effect of Vitamin D3 in combination with Omega‐3 Polyunsaturated Fatty Acids on NETosis in Type 2 Diabetes Mellitus Patients

Basyreva

Вахрушева

Леткеман

et al. 2021

Oxidative Medicine and Cellular Longevity

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An understanding of the consequences of oxidative/halogenative stress triggered by neutrophil activation is impossible without considering NETosis. NETosis, formation of neutrophil extracellular traps (NETs), is known to promote microthrombus formation and impair wound healing in type 2 diabetes mellitus (T2DM) patients. Therefore, there is a need to search for drugs and treatment approaches that could prevent excessive NET formation. We aimed to evaluate the effect of vitamin D3 in combination with omega-3 polyunsaturated fatty acids (vitamin D3/omega-3 PUFAs) on NETosis in T2DM patients with purulent necrotizing lesions of the lower extremities. Patients and healthy subjects had vitamin D3 deficiency. Patients received, beyond standard treatment, 6000 IU of vitamin D3 and 480 mg of omega-3 PUFAs, and healthy subjects 1000 IU of vitamin D3 and 240 mg of omega-3 PUFAs daily for seven days. Neutrophil activation in ex vivo blood by phorbol-12-myristate-13-acetate (PMA) was used as a NETosis model. The percentage of blood NETs relative to leukocytes (NETbackground) before vitamin D3/omega-3 PUFA supplementation was 3.2%-4.9% in healthy subjects and 1.7%-10.8% in patients. These values rose, respectively, to 7.7%-9.1% and 4.0%-17.9% upon PMA-induced NETosis. In addition, the leukocyte count decreased by 700-1300 per 1 μL in healthy subjects and 700-4000 per 1 μL in patients. For both patients and healthy subjects, taking vitamin D3/omega-3 PUFAs had no effect on NETbackground but completely inhibited PMA-induced NET formation, though neutrophils exhibited morphological features of activation. Also, leukocyte loss was reduced (to 500 per 1 μL). For patients on standard treatment alone, changes occurred neither in background NETs and leukocytes nor in their amount after PMA stimulation. The decreased ability of neutrophils to generate NETs, which can be achieved by vitamin D3/omega-3 PUFA supplementation, could have a positive effect on wound healing in T2DM patients and reduce the incidence and severity of complications.

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Section: Discussionmentioning

confidence: 98%