1. Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia 2. Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia; Institute of Experimental Medicine, Saint-Petersburg, Russia 3. Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia; State Research Institute of Highly Pure Biopreparations, Saint-Petersburg, Russia
Oxidative stress and neutrophil activation leading to an increase in myeloperoxidase (MPO), elastase and neutrophil extracellular trap (NET) levels in blood are considered as 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 length of the initial phase of wound healing (the inflammatory phase) in T2DM patients. Patients were divided retrospectively into three groups depending on the damage extent: group 1 (wound on toe) < group 2 (wound on foot) < group 3 (wound on lower leg). Compared to the control group (healthy volunteers), T2DM patients at admission to hospital had significantly (p<0.05) increased 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). The length of hospital stay after surgical procedures 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, p<0.05), and it was significantly higher for groups 2 and 3 compared to the control group and group 1. The neutrophil count before surgery in T2DM patients with damage in the lower extremities correlated with the length of the inflammatory phase of wound healing. The correlation found can be attributed to an increase in extracellular MPO and NETs, which, in its turn, results from 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.
Mikhalchik E.V. et al. Neutrophils as a source of factors that increase the length of the inflammatory phase of wound healing in patients with type 2 diabetes mellitus // Biomeditsinskaya khimiya. - 2018. - V. 64. -N 5. - P. 433-438.
Mikhalchik E.V. et al., "Neutrophils as a source of factors that increase the length of the inflammatory phase of wound healing in patients with type 2 diabetes mellitus." Biomeditsinskaya khimiya 64.5 (2018): 433-438.
Mikhalchik, E. V., Maximov, D. I., Ostrovsky, E. M., Yaskevich, A. V., Vlasova, I. I., Vakhrusheva, T. V., Basyreva, L. Yu., Gusev, A. A., Kostevich, V. A., Gorbunov, N. P., Sokolov, A. V., Panasenko, O. M., Gusev, S. A. (2018). Neutrophils as a source of factors that increase the length of the inflammatory phase of wound healing in patients with type 2 diabetes mellitus. Biomeditsinskaya khimiya, 64(5), 433-438.
Ostrovskij V.K., Svitich Yu.N. (1983) Vestnik khirurgii im. I.I. Grekova, 131(11), 21-24. Scholar google search
Wong S.L., Demers M., Martinod K., Gallant M., Yanming W., Goldfine A.B., Kahn C.R., Wagner D.D. (2015) Nat. Med., 21(7), 815-819. CrossRef Scholar google search
Fadini G.P., Menegazzo L., Rigato M., Scattoloini 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., Avogaro A. (2016) Diabetes, 65(4), 1061-1071. CrossRef Scholar google search
14. Basyreva L., Brodsky I., Gusev A., Zhapparova O., Mikhalchik E., Gusev S., Shor D., Dahan S., Blank M., Shoenfeld Y. (2015/2016) Human Antibodies, 24(3-4), 39-44. CrossRef Scholar google search