PGE2suppresses mitogen-induced Ca2+mobilization in T cells

Abstract

PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+signaling. The present study evaluated the effects of PGE2on 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+]iwas recorded in ∼60% of the cells. The pretreatment of T cells with PGE2had no apparent effect on [Ca2+]iin resting cells; it significantly suppressed the Con A-induced increase in [Ca2+]iin 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+]iwas dependent on Ca2+influx through the plasma membrane. Our data suggest that PGE2causes an overall suppression of the Con A-induced [Ca2+]ielevation in T cells via inhibiting both Ca2+influx and its release from the intracellular stores.