Published online before print March 10, 2009

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0408251

Received for publication April 18, 2008.
Revised February 4, 2009.
Accepted for publication February 14, 2009.

Article

Lymphocytes from P2X₇-deficient mice exhibit enhanced P2X₇ 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 ^¶, and James I. Elliott ^**@

*MRC Clinical Sciences Centre and **Department of Molecular Genetics and Rheumatology, Division of Medicine, and ^¶Imperial College Kidney and Transplant Institute, Imperial College London, London, United Kingdom; Centers for Oral Biology and Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York, USA; and Neurosciences Centre of Excellence for Drug Discovery and ^||Transgenic Technologies, Molecular Discovery Research, GlaxoSmithKline R & D Limited, Harlow, Essex, United Kingdom

^@ To whom correspondence should be addressed. E-mail: james.elliott{at}imperial.ac.uk.

Abstract

The purinergic receptor P2X₇ is expressed on immune cells, and its stimulation results in the release of IL-1 from macrophages. Its absence, as evidenced from the analysis of two independent strains of P2X₇-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.

Key Words: inflammation • P2 receptors • rodent • transgenic/knock-out mice

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