Hypertonic stress regulates T cell function via pannexin-1 hemichannels and P2X receptors.
J Leukoc Biol
; 88(6): 1181-9, 2010 Dec.
Article
em En
| MEDLINE
| ID: mdl-20884646
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Solução Salina Hipertônica
/
Estresse Fisiológico
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Linfócitos T
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Conexinas
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Receptores Purinérgicos P2X
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Proteínas do Tecido Nervoso
Limite:
Humans
Idioma:
En
Revista:
J Leukoc Biol
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos