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S. R. Taylor, J. I. Elliott; The P2X7 Receptor in Ocular Inflammatory Disease. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5196.
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The P2X7 receptor is one of a family of purinergic receptors abundant in several human tissues including cells of the immune system. Cellular activation via this receptor results in cytokine and chemokine release and immune cell signalling, but prolonged stimulation leads to cell death. It has been detected on retinal microvasculature but its role is unknown. It may be a mediator of cell death following pathological insults. We induced cell death by stimulation of the P2X7 receptor on murine T-cells to determine whether this was apoptotic in type or whether cell necrosis ensued. We also examined its distribution in normal and inflammatory orbital tissue.
T-lymphocytes were isolated from mesenteric lymph node dissections of BALB/c mice, stained with appropriate fluorescently-conjugated antibodies and analysed by flow cytometry and live-cell microscopy with time-lapse fluorescence photography.Paraffin-embedded mouse tissues and human orbital biopsies taken in the presence and absence of autoimmune disease were obtained for immunohistochemical analysis with commercially-available P2X7 antibodies.
Stimulation of the P2X7 receptor with the specific agonist BzATP led to a sequence of rapid cell shrinkage followed by cell swelling above baseline culminating in rapid, lytic cell death after approximately 10-30 minutes. Immunohistochemical analysis revealed widespread distribution of the P2X7R in both human and mouse tissues and evidence of increased expression in the presence of autoimmune disease.
Although there is overlap between some the features of apoptosis and necrosis, the associated changes in cell size are distinct, with apoptotic cell death being associated with cell shrinkage and necrotic cell death with cell swelling. The P2X7 death pathway, however, involves waves of cell shrinkage and swelling that has features of both apoptosis and necrosis. The presence of the receptor in different tissues and evidence of increased expression in autoimmune disease suggest it may play an important role in systemic disease susceptibility and course.
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