Abstract
This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5′-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells.
Highlights
Purinergic signalling in the main subsets of immune cellsPolymorphonuclear leukocytes Neutrophils Eosinophils Basophils Mast cells Section summaryMonocytes, macrophages and microglia Monocytes Macrophages Microglia Section summaryDendritic cells P1 receptors P2 receptors Section summaryLymphocytes T and B lymphocytes Natural killer (NK and NKT) cells Section summary
Nucleotides, such as adenosine 5′-triphosphate (ATP) and uridine 5′-triphosphate (UTP), are mainly intracellular, they are released into the extracellular fluids by various mechanisms
In vivo an upregulation of P2Y6 was observed following administration of kainic that damages neurons, leading to microglia activation. Taken together these findings show that adenosine 5′diphosphate (ADP), acting through P2Y12, is a find-me signal for microglia, whereas UDP, acting on P2Y6, behaves as an eat-me signal [344] (Fig. 5)
Summary
Purinergic signalling in the main subsets of immune cellsPolymorphonuclear leukocytes Neutrophils Eosinophils Basophils Mast cells Section summaryMonocytes, macrophages and microglia Monocytes Macrophages Microglia Section summaryDendritic cells P1 receptors P2 receptors Section summaryLymphocytes T and B lymphocytes Natural killer (NK and NKT) cells Section summary. P1 receptors Adenosine was initially reported to inhibit the production of the second complement component (C2) of human monocytes [185], and this effect was later shown to be mediated by A2 receptors [186].
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