PGE₂ suppresses Ca²⁺ influx but not intracellular Ca2 release in rat T-cells

T-lymphocyte proliferation is important in the generation of immune response. It is induced by antigens which cause a sustained elevation of intracellular Ca2 (Cai) leading to production and secretion of IL-2, a cytokine which is essential for proliferation. During burn and sepsis, T-cell proliferation is inexplicably suppressed, a response which is due at least in part to systemic elevation of prostaglandin E2 (PGE2). We have shown recently that PGE? suppresses the sustained Caj elevation induced by the mitogen concanavalin A (conA) in rat Tlymphocytes measured with fura-2 spectroscopy (Choudhry, Ahmad and Sayeed, Infection & Immunity 63:3101-3105, 1995). Since Ca, elevation can result from Ca influx through the plasma membrane as well as release from intracellular stores, we re-examined the responses to conA and PGE2 in the presence of 3 mM EGTA which eliminated Ca influx. In EGTA, the Ca response to conA was reduced 50% but unlike the sustained elevation of Ca, in the absence of EGTA, Ca-4 returned to basal level despite the continued presence of conA. In EGTA, PGEj also induced a transient elevation of C-4 similar to conA indicating that PGE, suppression in normal solution was due to inhibition of Ca influx and not to inhibition of intracellular Ca release mechanisms. These results support studies showing that PGE2 has multiple sites of action in T-lymphocytes, and it provides further evidence that PGE, contributes to immunosuppression. (Supported in part by NIH grants GM-53235 & GM-32288 to MMS and the Falk Foundation to MAC).