Hypertonic stress regulates T cell function via pannexin-1 hemichannels and P2X receptors
Open Access
- 30 September 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 88 (6), 1181-1189
- https://doi.org/10.1189/jlb.0410211
Abstract
Hypertonic stress activates T cells by inducing the controlled release of ATP through pannexin-1 hemichannels and activation of ATP-gated ion channels P2X1, P2X4, and P2X7. Hypertonic saline (HS) resuscitation increases T cell function and inhibits posttraumatic T cell anergy, which can reduce immunosuppression and sepsis in trauma patients. We have previously shown that HS induces the release of cellular ATP and enhances T cell function. However, the mechanism by which HS induces ATP release and the subsequent regulation of T cell function by ATP remain poorly understood. In the present study, we show that inhibition of the gap junction hemichannel pannexin-1 (Panx1) blocks ATP release in response to HS, and HS exposure triggers significant changes in the expression of all P2X-type ATP receptors in Jurkat T cells. Blocking or silencing of Panx1 or of P2X1, P2X4, or P2X7 receptors blunts HS-induced p38 MAPK activation and the stimulatory effects of HS on TCR/CD28-induced IL-2 gene transcription. Moreover, treatment with HS or agonists of P2X receptors overcomes T cell suppression induced by the anti-inflammatory cytokine IL-10. These findings indicate that Panx1 hemichannels facilitate ATP release in response to hypertonic stress and that P2X1, P2X4, and P2X7 receptor activation enhances T cell function. We conclude that HS and P2 receptor agonists promote T cell function and thus, could be used to improve T cell function in trauma patients.Keywords
Funding Information
- National Institutes of Health (R01 GM-51477, GM-60475, AI-072287, R01 AI-080582)
- DOD/CDMRP (PR043034)
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