Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses.
The purinergic receptor P2X(7) is expressed on immune cells, and its stimulation results in the release of IL-1beta 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, P2X(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(7) antibodies staining brain tissue from both strains of P2X(7)(-/-) mice identically to wild-type mice. It has therefore been suggested that neurons express a distinct "P2X(7)-like" protein that has similar antibody recognition epitopes to P2X(7) and some properties of the genuine receptor. In this study, we show that whereas P2X(7) activity is absent from macrophages and dendritic cells in P2X(7)(-/-) animals, T cells from one gene-deficient strain unexpectedly exhibit higher levels of P2X(7) activity than that found in cells from control, unmanipulated C57BL/6 mice. A potential mechanism for this tissue-specific P2X(7) expression in P2X(7)(-/-) animals is discussed, as is the implication that the immune and indeed neuronal functions of P2X(7) may have been underestimated.
Taylor
Simon R J
SR
Division of Medicine, Imperial College, Hammersmith Hospital, Du Cane Rd., London W12 0NN, UK.
Gonzalez-Begne
Mireya
M
Sojka
Dorothy K
DK
Richardson
Jill C
JC
Sheardown
Steven A
SA
Harrison
Stephen M
SM
Pusey
Charles D
CD
Tam
Frederick W K
FW
Elliott
James I
JI
D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D018390:Gene Targeting; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D001616:beta-Galactosidase / Q000378:metabolism
C548227:P2rx4 protein, mouse; C546469:P2rx7 protein, mouse; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D058848:Receptors, Purinergic P2X4; D058486:Receptors, Purinergic P2X7; D001616:beta-Galactosidase