P2X7 receptor polymorphism impairs extracellular adenosine 5'-triphosphate-induced interleukin-18 release from human monocytes.
Interleukin (IL)-18 is an important proinflammatory cytokine processed and released from cells of the monocyte lineage by activation of the P2X(7) receptor by extracellular adenosine 5'-triphosphate (ATP). We examined if a loss-of-function polymorphism of the human P2X(7) receptor (glutamic acid-496 to alanine) impairs this process. Using a whole blood-based assay, ATP-induced release of IL-18 from homozygous subjects after 120 min incubation with ATP was 42% of that from wild-type subjects. Moreover, the level of ATP-induced IL-18 release from lipopolysaccharide (LPS)-primed monocytes of homozygous subjects after 30 and 60 min incubation with ATP was 21 and 44%, respectively, of that from wild-type monocytes. Nigericin, a K(+) ionophore, induced a similar release of IL-18 from monocytes of either genotype. ATP-induced ethidium(+) uptake in LPS-primed, monocytes of homozygous subjects was only 11% of that in wild-type monocytes, while P2X(7) surface expression on LPS-primed, homozygous monocytes was 44% of that on wild-type monocytes.
Sluyter
R
R
Department of Medicine, University of Sydney at Nepean Hospital, Penrith NSW 2750, Australia. rons@med.usyd.edu.au
Dalitz
J G
JG
Wiley
J S
JS
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D018048:Receptors, Purinergic P2 / Q000235:genetics*; D058486:Receptors, Purinergic P2X7
D020382:Interleukin-18; C546468:P2RX7 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate