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P2X7 receptor polymorphism impairs extracellular adenosine 5′-triphosphate-induced interleukin-18 release from human monocytes

Genes & Immunity volume 5, pages 588–591 (2004)Cite this article

Abstract

Interleukin (IL)-18 is an important proinflammatory cytokine processed and released from cells of the monocyte lineage by activation of the P2X7 receptor by extracellular adenosine 5′-triphosphate (ATP). We examined if a loss-of-function polymorphism of the human P2X7 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 P2X7 surface expression on LPS-primed, homozygous monocytes was 44% of that on wild-type monocytes.

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Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia and the Leukaemia Foundation of Australia. We thank Dr Stephen Fuller for coordinating the collection of some blood samples, Dr Ben Gu for preparation of the anti-P2X7 antibody and Ms Anne Shemon for critically reviewing the manuscript.

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Authors and Affiliations

  1. Department of Medicine, University of Sydney at Nepean Hospital, Penrith, 2750, NSW, Australia

    R Sluyter, JG Dalitz & JS Wiley

  2. Department of Pathology, Nepean Hospital, Penrith, 2750, NSW, Australia

    JS Wiley

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  1. R Sluyter
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Correspondence to R Sluyter.

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Sluyter, R., Dalitz, J. & Wiley, J. P2X7 receptor polymorphism impairs extracellular adenosine 5′-triphosphate-induced interleukin-18 release from human monocytes. Genes Immun 5, 588–591 (2004). https://doi.org/10.1038/sj.gene.6364127

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