Lymphocytes from P2X sub(7)-deficient mice exhibit enhanced P2X sub(7) responses

• Published in: Journal of leukocyte biology Vol. 85; no. 6; pp. 978 - 986
• Main Authors: Taylor, SRJ, Gonzalez-Begne, M, Sojka, D K, Richardson, J C, Sheardown, SA, Harrison, S M, Pusey, C D, Tam, FWK, Elliott, JI
• Format: Journal Article
• Language: English
• Published: 01.06.2009
• ISSN: 0741-5400

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