Induction of responsiveness to interleukin 2 in mouse lymphocytes by synergistic action of ionophore A 23187 and diacylglycerol.

We investigated whether the protein kinase C-binding agents 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and 1-oleoyl-2-acetyl-rac-glycerol (OAG) induced reactivity to interleukin 2 (IL-2) in mouse lymphocytes. 10(-8) M TPA was a strong inducer of reactivity to IL-2 measured by [3H]thymidine incorporation. In contrast OAG alone (6-25 micrograms/ml) did not induce a significant IL-2 mediated proliferative response. Cells stimulated with the ionophore A 23187 + OAG neither proliferated nor produced IL-2. In contrast, cells stimulated with A 23187 + OAG + IL-2 showed a significant proliferative response, indicating the expression of functional high affinity IL-2 receptors. The expression of reactivity to IL-2 induced by A 23187 + OAG was inhibited by 0.04 mM Mn2+; in contrast the TPA-mediated induction of IL-2 responsiveness was not affected by Mn2+. The data suggest differences in the mechanism of induction of IL-2 responsiveness by the two protein kinase C-binding agents, TPA and OAG.