Purinergic Regulation of Neutrophil Function

Abstract

Purinergic signaling, which utilizes nucleotides (particularly ATP) and adenosine as transmitter molecules, plays an essential role in immune system. In the extracellular compartment, ATP predominantly functions as a pro-inflammatory molecule through activation of P2 receptors, whereas adenosine mostly functions as an anti-inflammatory molecule through activation of P1 receptors. Neutrophils are the most abundant immune cells in circulation and have emerged as an important component in orchestrating a complex series of events during inflammation. However, because of the destructive nature of neutrophil-derived inflammatory agents, neutrophil activation is fine-tuned, and purinergic signaling is intimately involved in this process. Indeed, shifting the balance between P2 and P1 signaling is critical for neutrophils to appropriately exert their immunologic activity. Here, we review the role of purinergic signaling in regulating neutrophil function, and discuss the potential of targeting purinergic signaling for the treatment of neutrophil-associated infectious and inflammatory diseases.

Relief of tumor hypoxia unleashes the tumoricidal potential of neutrophils

“…Similarly, altered PMN effector function under hypoxic conditions might reflect in part the direct effects of hypoxia on PMN degranulation and respiratory burst activity, as described above, but also its indirect effects as mediated through other cell types. For example, extracellular adenosine, which is generated in the hypoxic tumor microenvironment (55), can inhibit PMN respiratory burst activity (56). Further work will be necessary to determine the identity and relative importance of these intrinsic and extrinsic pathways over the control of tumor-associated PMN phenotypes.…”

Adenosine Signaling in Autoimmune Disorders

“…Ado also regulates the activation of neutrophils, the most abundant leukocytes acting as a first line of defense of the innate immunity. Neutrophils also express both CD39 and CD73 enzymes and represent an abundant source of Ado, which in turn regulates their activation under both normal and inflammatory conditions [15], acting on its four receptors that are all expressed by this cell population [16]. In particular, A 1 ARs promote neutrophil chemotaxis, while A 2A AR and A 2B AR activation inhibit neutrophils' adhesion to endothelial cells [2].…”

Trypanosoma brucei brucei Induces Polymorphonuclear Neutrophil Activation and Neutrophil Extracellular Traps Release

“…Data on metabolic requirements of PMN during parasitetriggered NETs formation are limited (31). Nevertheless, it is known that extracellular adenosine 5 ′ -triphospate (ATP) availability and activation of P2 purinergic receptors play fundamental roles in PMN activation (31).…”

“…Data on metabolic requirements of PMN during parasitetriggered NETs formation are limited (31). Nevertheless, it is known that extracellular adenosine 5 ′ -triphospate (ATP) availability and activation of P2 purinergic receptors play fundamental roles in PMN activation (31). Thus, P2-mediated purinergic signaling pathways are involved in the regulation of essential functions of PMN, such as chemotaxis, phagocytosis, oxidative burst, degranulation (31).…”