PGE2 suppresses mitogen-induced Ca2+ mobilization in T cells.
PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE2 on Ca2+ release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+ concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+ imaging technique, and the release of Ca2+ from intracellular stores and Ca2+ influx were spectrofluorometrically quantified in T cell suspensions. Under unstimulated conditions, nearly 85% of T cells exhibited [Ca2+]i </=50 nM. After stimulation with concanavalin A (Con A), an increase in [Ca2+]i was recorded in approximately 60% of the cells. The pretreatment of T cells with PGE2 had no apparent effect on [Ca2+]i in resting cells; it significantly suppressed the Con A-induced increase in [Ca2+]i in all of the Con A-responsive cells. Ca2+ release from the intracellular stores contributed to the early spike in [Ca2+]i, and the late phase of elevation in [Ca2+]i was dependent on Ca2+ influx through the plasma membrane. Our data suggest that PGE(2) causes an overall suppression of the Con A-induced [Ca2+]i elevation in T cells via inhibiting both Ca2+ influx and its release from the intracellular stores.
Choudhry
M A
MA
Trauma/Critical Care Research Laboratories, Departments of Surgery and Physiology, Burn & Shock Trauma Institute, Loyola University Chicago Medical Center, Maywood, Illinois 60153, USA.
Hockberger
P E
PE
Sayeed
M M
MM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004533:Egtazic Acid / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*
D003208:Concanavalin A; D004533:Egtazic Acid; D015232:Dinoprostone; D002118:Calcium