Hypertonic stress increases T cell interleukin-2 expression through a mechanism that involves ATP release, P2 receptor, and p38 MAPK activation.
Hypertonic stress (HS) can alter the function of mammalian cells. We have reported that HS enhances differentiated responses of T cells by increasing their ability to produce interleukin (IL)-2, a finding of clinical interest because hypertonic infusions may modulate immune function in patients. HS shrinks cells and mechanically deforms membranes, which results in ATP release from many cell types. Here we investigate if ATP release is an underlying mechanism through which HS augments T cell function. We found that mechanical stress and HS induced rapid ATP release from Jurkat T cells. HS and exogenous ATP mobilized intracellular Ca(2+), activated p38 MAPK, and increased IL-2 expression. Ca(2+) mobilization was attenuated in the presence of EGTA or by removal of extracellular ATP with apyrase. Adenosine did not increase IL-2 expression, as did ATP. Apyrase, inhibition of P2 receptors, or inhibition of p38 MAPK with SB203580 reduced the stimulatory effects of HS, indicating that HS enhances IL-2 expression through a mechanism that involves ATP release, P2 (perhaps P2X7) receptors, and p38 MAPK activation. We conclude that release of and response to ATP plays a key role in the mechanism through which hypertonic stress regulates the function of T cells.
Loomis
William H
WH
Department of Surgery/Trauma, University of California San Diego Medical Center, San Diego, California 92103, USA.
Namiki
Sachiko
S
Ostrom
Rennolds S
RS
Insel
Paul A
PA
Junger
Wolfgang G
WG
D000255:Adenosine Triphosphate / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D006982:Hypertonic Solutions; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009997:Osmotic Pressure; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D006982:Hypertonic Solutions; D007376:Interleukin-2; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases