Arginine is essential in reversing prostaglandin E(2) T-cell suppression by hypertonic saline.
BACKGROUND
T-cell dysfunction after trauma is characterized by decreased T-cell proliferation. Hypertonic saline (HS) restores T-cell proliferation by an unknown mechanism. Arginine and regulation of arginine metabolism plays an important role in normal T-cell function. We hypothesize that HS restoration of T-cell dysfunction is dependent on an arginine mediated mechanism.


METHODS
Jurkat cells were cultured in both 0 mM and 1.14 mM arginine media. Cell proliferation was suppressed using prostaglandin E2 (PGE(2)) and treated with HS at 20 and 40 mM above isotonicity. Arginase activity was blocked by norNOHA. Cell proliferation, arginase activity, and nitrite accumulation were measured.


RESULTS
PGE(2) caused a 15.0% inhibition of Jurkat cell proliferation compared with control (P<0.05). HS reversed PGE(2) suppressed Jurkat cell proliferation to normal. PGE(2) suppression decreased mean arginase activity (66.5+/-15 nmol/min/mg) compared with controls (98.4+/-14 nmol/min/mg) (P<0.05). Cells treated with HS had higher arginase activity (123.8+/-38 nmol/min/mg) then PGE(2) suppressed cells and controls (P <.05). Conversely, nitrite was decreased by 14.5% +/- 3.1% in HS treated cells compared with PGE(2) suppression (P<0.05). HS did not restore PGE(2) cell suppression when arginase I was blocked by norNOHA, nor when cells were cultured in arginine-free media.


CONCLUSIONS
Arginine is essential in restoring Jurkat cell proliferation by HS. HS may restore T-cell dysfunction by increasing arginine transport and arginine metabolism by arginase I. HS treatment will not restore suppressed T-cell proliferation without adequate extracellular concentrations of arginine.
Choi
Sung Hyuk
SH
Department of Emergency Medicine, College of Medicine, Korea University, Seoul, Korea.
Bansal
Vishal
V
Costantini
Todd
T
Putnam
Jim
J
Loomis
William
W
Coimbra
Raul
R
D001119:Arginase / Q000378:metabolism; D001120:Arginine / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D009573:Nitrites; D012462:Saline Solution, Hypertonic; D001120:Arginine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D001119:Arginase; D015232:Dinoprostone