Abstract
Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential not only for energy usage, but also for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). It has been demonstrated that activated viable neutrophils can produce NETs, which consists of a DNA scaffold able to bind granule proteins and microorganisms. The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and therefore energy-dependent process. In this article, we discuss the glycolytic and other metabolic routes in association with neutrophil functions focusing on their role for building up NETs in the extracellular space. A better understanding of the requirements of metabolic pathways for neutrophil functions may lead to the discovery of molecular targets suitable to develop novel anti-infectious and/or anti-inflammatory drugs.
Highlights
Neutrophils are the most abundant white blood cells in the human peripheral blood with an estimated daily turnover of 1010 to 1011 cells [1, 2]
The role of the metabolism of fatty acids on neutrophil extracellular traps (NETs) formation is less studied, it has been reported that non-esterified fatty acids (NEFAs) such as oleic acid (OA) and linoleic acid (LA), that are often associated with infectious diseases, are associated with a higher incidence of infections and NEFAs induced the formation of NETs through extracellular release of adenosine triphosphate (ATP) via Pannexin 1 and subsequent activation of purinergic receptors
Neutrophils are capable of adapting to the tissue environment under pathological conditions by modifying their metabolic activity utilizing several metabolic pathways
Summary
Neutrophils are the most numerous cells in the leukocyte population and essential for innate immunity. To limit their effector functions, neutrophils are able to modulate glycolysis and other cellular metabolic pathways. These metabolic pathways are essential for energy usage, and for specialized effector actions, such as the production of reactive oxygen species (ROS), chemotaxis, phagocytosis, degranulation, and the formation of neutrophil extracellular traps (NETs). The formation of NETs requires the availability of increased amounts of adenosine triphosphate (ATP) as it is an active cellular and energy-dependent process.
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