P2 purinoceptors in the immune system.
Immune cells express plasma membrane receptors for extracellular nucleotides. Both G protein-linked metabotropic and channel-forming ionotropic receptors have been described, although no P2 receptor subtype has been cloned from the immune system thus far. Metabotropic receptors have been described in human B but not T lymphocytes; they have not been found in mouse B and T cells. Ionotropic receptors seem to be ubiquitously expressed in the immune system; however, their functional properties, if not their pharmacology, appear to be different in different immune cells. Human T normal and B leukaemic lymphocytes, human macrophages, mouse B and T lymphocytes, mouse microglial and macrophage cells, and rat mast cells express ionotropic receptors that recognize ATP4- as the preferred ligand, are activated by 3'-O-(4-benzoyl)benzoyl ATP and inhibited by oxidized ATP. The pharmacological profile of ionotropic receptors expressed by different immune cells is similar, but their permeability properties may be different: the pore formed by receptors expressed by macrophages, microglial cells and mast cells is typically permeable to charged molecules of molecular mass up to 900 Da; on the contrary, that expressed by lymphocytes has a molecular cut-off of 200-300 Da. The ionotrpic receptor of immune cells is modulated by inflammatory cytokines (e.g. interleukin [IL]-2 and gamma-interferon) and is also modulated during monocyte to macrophage differentiation. Transient stimulation of the ionotropic receptor of macrophages and microglial cells elicits IL-1 beta release. Sustained activation leads to cell death, either by necrosis or apoptosis, depending on the given cell type.
Di Virgilio
F
F
Institute of General Pathology, University of Ferrara, Italy.
Ferrari
D
D
Falzoni
S
S
Chiozzi
P
P
Munerati
M
M
Steinberg
T H
TH
Baricordi
O R
OR
D000818:Animals; D016923:Cell Death / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology; D018048:Receptors, Purinergic P2 / Q000276:immunology*; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2
C546468:P2RX7 protein, human; C546385:P2RY2 protein, human; C546469:P2rx7 protein, mouse; C546470:P2rx7 protein, rat; C546386:P2ry2 protein, mouse; C546387:P2ry2 protein, rat; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D058473:Receptors, Purinergic P2Y2