P2X7 receptor and macrophage function

Abstract

Macrophages are unique innate immune cells that play an integral role in the defense of the host by virtue of their ability to recognize, engulf, and kill pathogens while sending out danger signals via cytokines to recruit and activate inflammatory cells. It is becoming increasingly clear that purinergic signaling events are essential components of the macrophage response to pathogen challenges and disorders such as sepsis may be, at least in part, regulated by these important sensors. The activation of the P2X 7 receptor is a powerful event in the regulation of the caspase-1 inflammasome. We provide evidence that the inflammasome activation requires "priming" of macrophages prior to ATP activation of the P2X 7 R. Inhibition of the inflammasome activation by the tyrosine kinase inhibitor, AG126, suggests regulation by phosphorylation. Finally, the P2X 7 R may also be activated by other elements of the host response such as the antimicrobial peptide LL-37, which adds a new, physiologically relevant agonist to the P2X 7 R pathway. Therapeutic approaches to inflammation and sepsis will certainly be enhanced by an increased understanding of how purinergic receptors modulate the inflammasomes.

P2X ion channel receptors and inflammation

“…All immune cells, whether of the myeloid or lymphoid lineage, express at least one P2X receptor subtype, and many express all seven subtypes [2,45,[76][77][78][79][80][81]. Mononuclear phagocytes are the inflammatory cell type where P2X receptor expression has been best characterized [82].…”

P2X7 Receptor Expression in Peripheral Blood Monocytes Is Correlated With Plasma C-Reactive Protein and Cytokine Levels in Patients With Type 2 Diabetes Mellitus: a Preliminary Report

“…There are two P2 receptor subfamilies, P2X cation channel-and P2Y G-proteincoupled receptors. At least eight P2Y family members (P2Y 1-2 , P2Y 4 , P2Y 6 , P2Y [11][12][13][14] and seven P2X receptors (P2X 1-7 ) have been described. P2X 7 receptor induction has been implicated in a variety of inflammatory conditions [8].…”

Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation

“…Such a direct interaction with P2 receptors has recently been proposed for the antimicrobial peptide LL-37 (66), and reports on the P2R and EGFR-activation properties of this peptide are of particular interest here (67,68). There is evidence that the peptide induces IL-1␤ release in lipopolysaccaride-primed monocytes through activation of P2X7 (64).…”