PGE2 suppresses mitogen-induced Ca2+ mobilization in T cells

PGE(2)-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE(2) 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) less than or equal to 50 nM. After stimulation with concanavalin A (Con A), an increase in [Ca2+](i) was recorded in similar to 60% of the cells. The pretreatment of T cells with PGE(2) 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.