Hypertonic stress regulates T-cell function by the opposing actions of extracellular adenosine triphosphate and adenosine.
Hypertonic saline (HS) treatment promotes interleukin (IL)-2 production and enhances T-cell activation by the release of cellular adenosine triphosphate (ATP) that activates P2 nucleotide receptors. Released ATP can be hydrolyzed to adenosine, which inhibits T-cell activation. We examined if adenosine affects the response of T cells to HS treatment, and found that the amount of ATP released from T cells is a function of the HS concentration and duration of HS exposure. Physiologically relevant HS concentrations (<40 mmol/L) induced rapid ATP release, with the highest ATP concentrations released within 1 min. The released ATP was converted to adenosine, which opposed the enhancing effects of HS on IL-2 production. We found that Jurkat and CD4+ primary human T cells express most abundantly the A2A and A2B adenosine receptor subtypes, which mediate the suppressive effects of adenosine, as the A2 receptor agonist CGS 21680 suppressed IL-2 production, whereas the A2 receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine augmented the enhancing effect of HS on T-cell function. Elimination of extracellular adenosine by adding exogenous adenosine deaminase also increased the enhancing effects of HS. These data suggest that the effect of HS treatment on T-cell function can be modulated with pharmacological agents that abolish the suppressive effects of adenosine formed from the ATP that is released in response to HS treatment.
Yip
Linda
L
Surgical Immunology Research Laboratory, Department of Surgery, Division of Trauma, University of California San Diego, San Diego, California 92103-8236, USA.
Cheung
Cindy W
CW
Corriden
Ross
R
Chen
Yu
Y
Insel
Paul A
PA
Junger
Wolfgang G
WG
D000241:Adenosine / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D002469:Cell Separation; D006801:Humans; D006868:Hydrolysis; D007376:Interleukin-2 / Q000378:metabolism; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008954:Models, Biological; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D013312:Stress, Physiological / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
D007376:Interleukin-2; D018047:Receptors, Purinergic P1; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase; D000241:Adenosine