Lymphocytes from P2X7-deficient mice exhibit enhanced P2X 7 responses

Simon R.J. Taylor, Mireya Gonzalez-Begne, Dorothy K. Sojka, Jill C. Richardson, Steven A. Sheardown, Stephen M. Harrison, Charles D. Pusey, Frederick W.K. Tam, James I. Elliott

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Abstract

The purinergic receptor P2X7 is expressed on immune cells, and its stimulation results in the release of IL-1β from macrophages. Its absence, as evidenced from the analysis of two independent strains of P2X 7-deficient mice, results in reduced susceptibility to inflammatory disease, and the molecule is an important, potential therapeutic target in autoimmunity. However, P2X7 has also been detected in several neuronal cell types, although its function and even its presence in these cells are highly contested, with anti-P2X7 antibodies staining brain tissue from both strains of P2X7-/- mice identically to wild-type mice. It has therefore been suggested that neurons express a distinct "P2X7-like" protein that has similar antibody recognition epitopes to P2X7 and some properties of the genuine receptor. In this study, we show that whereas P2X7 activity is absent from macrophages and dendritic cells in P2X7-/- animals, T cells from one gene-deficient strain unexpectedly exhibit higher levels of P2X7 activity than that found in cells from control, unmanipulated C57BL/6 mice. A potential mechanism for this tissue-specific P2X7 expression in P2X7-/- animals is discussed, as is the implication that the immune and indeed neuronal functions of P2X7 may have been underestimated.

Original languageEnglish
Pages (from-to)978-986
Number of pages9
JournalJournal of Leukocyte Biology
Volume85
Issue number6
DOIs
StatePublished - Jun 1 2009

Keywords

  • Inflammation
  • P2 receptors
  • Rodent
  • Transgenic/knock-out mice

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    Taylor, S. R. J., Gonzalez-Begne, M., Sojka, D. K., Richardson, J. C., Sheardown, S. A., Harrison, S. M., Pusey, C. D., Tam, F. W. K., & Elliott, J. I. (2009). Lymphocytes from P2X7-deficient mice exhibit enhanced P2X 7 responses. Journal of Leukocyte Biology, 85(6), 978-986. https://doi.org/10.1189/jlb.0408251