Neutrophil dysfunction induced by hyperglycemia: modulation of myeloperoxidase activity

Abstract

Our data suggest that impaired activity of myeloperoxidase (MPO) may play an important role in the dysfunction of neutrophils from hyperglycemic rats. Neutrophil biochemical pathways include the NADPH oxidase system and the MPO enzyme. They both play important role in the killing function of neutrophils. The effect of hyperglycemia on the activity of these enzymes and the consequences with regard to Candida albicans phagocytosis and the microbicidal property of rat peritoneal neutrophils is evaluated here. The NADPH oxidase system activity was measured using chemiluminescence and cytochrome C reduction assays. MPO activity was measured by monitoring HOCl production, and MPO protein expression was analysed using Western blot and immunofluorescence. C. albicans phagocytosis and death were evaluated by optical microscopy using the May-Grunwald-Giemsa staining method. ROS generation kinetic was slightly delayed in the diabetic group. MPO expression levels were higher in diabetic neutrophils; however, MPO activity was decreased in these same neutrophils compared with the controls. C. albicans phagocytosis and killing were lower in the diabetic neutrophils. Based on our experimental model, the phagocytic and killing functions of neutrophil phagocytosis are impaired in diabetic rats because of the decreased production of HOCl, highlighting the importance of MPO in the microbicidal function of neutrophils.

High glucose modulates IL‐6 mediated immune homeostasis through impeding neutrophil extracellular trap formation

“…This suggests that high glucose-dependent priming of neutrophils produces superoxides constitutively and may contribute towards pre-activation of neutrophils. However, peritoneal neutrophils from alloxan induced diabetic rats showed impaired and delayed NADPH oxidase activity in response to Candida albicans infection [17], suggesting role of multiple mechanisms for neutrophil activation in T2D conditions.…”

“…Hyperglycemic conditions have been shown to attenuate LPS induced neutrophil degranulation resulting in a decreased release of myeloperoxidase and elastase from azurophilic granules. This suggests that increased circulating glucose under inflammatory conditions abrogates neutrophil degranulation [16,17]. Hence, to examine any modulation in NETs associated proteins in diabetic subjects, we measured elastase activity.…”

Neutrophil Extracellular Traps and Cardiovascular Diseases: An Update

“…Diabetes is characterized by a low-grade inflammation [39] explaining the typical complications of the disease through endothelial dysfunction, hyperreactivity of platelets, and elevated levels of pro-coagulant mediators [40,41]. Hyperglycemic conditions were reported to limit lipopolysaccharide (LPS)-induced neutrophil degranulation and the following release of granular proteins, i.e., MPO and NE [42,43]. In recent years, a progressive number of evidences shed light on the role played by neutrophils in the pathophysiology of diabetes (both type 1 diabetes [T1D] and type 2 diabetes [T2D]) [44][45][46][47].…”

The role of the microbiome in nonhealing diabetic wounds

“…It independently promotes the establishment of a microbiome by (1) creating a surplus nutrient source for bacteria and fungi and (2) decreasing innate immunity . Specifically, hyperglycemia leads to poor chemotaxis, phagocytosis, and lysis of bacteria and fungi by neutrophils due to low production of superoxide and myeloperoxidase . Peripheral neuropathy, including sensory, motor, and autonomic deficits, is an underlying comorbidity in the majority of ulcers .…”