Abstract
In addition to a fundamental role in cellular bioenergetics, the purine nucleotide adenosine triphosphate (ATP) plays a crucial role in the extracellular space as a signaling molecule. ATP and its metabolites serve as ligands for a family of receptors that are collectively referred to as purinergic receptors. These receptors were first described and characterized in the nervous system but it soon became evident that they are expressed ubiquitously. In the immune system, purinergic signals regulate the migration and activation of immune cells and they may also orchestrate the resolution of inflammation (1, 2). The intracellular signal transduction initiated by purinergic receptors is strongly coupled to Ca2+-signaling, and co-ordination of these pathways plays a critical role in innate immunity. In this review, we provide an overview of purinergic and Ca2+-signaling in the context of macrophage phenotypic polarization and discuss the implications on macrophage function in physiological and pathological conditions.
Highlights
In addition to a fundamental role in cellular bioenergetics, the purine nucleotide adenosine triphosphate (ATP) plays a crucial role in the extracellular space as a signaling molecule
Macrophages express a wide variety of P2X and P2Y receptors; analysis of mouse macrophages using a variety of techniques indicates the presence of P2X4, P2X7, P2Y1, P2Y2, P2Y4, and P2Y6 receptors [3]
A variety of inflammation-related biological processes result in ATP release from cells, and macrophages respond to this extracellular ATP rapidly
Summary
In addition to a fundamental role in cellular bioenergetics, the purine nucleotide adenosine triphosphate (ATP) plays a crucial role in the extracellular space as a signaling molecule. P2Y2 plays a crucial chemotactic role in locating apoptotic cells releasing ATP [9]. Activation of P2X7 by high concentrations of ATP mediates caspase-1-dependent cell death accompanied by the release of proinflammatory cytokines, such as IL-1β and IL-18.
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