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

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.