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Mitogenic action of phorbol ester TPA and calcium ionophore A23187 on human cord and maternal/adult peripheral lymphocytes: regulation by prostaglandin E2.

We have investigated the mitogenic action of the phorbol ester 12-O-tetrade-canoylphorbol-13-acetate (TPA) and the calcium ionophore A23187 on peripheral blood mononuclear leucocytes (PBML) from human neonates (cord), their mothers and other unrelated adults. TPA induced similar proliferation among maternal and unrelated adult PBML. In contrast, cord PBML regularly gave lower responses, on average 40-45% at optimal TPA concentration, than either maternal or other adult cells. A23187 had only a weak mitogenic effect on cord and maternal/adult cells. However, A23187 added together with TPA induced a strong proliferative response at low, non-mitogenic concentrations of either agent. Furthermore, TPA and the mitogenic OKT3 antibody showed a marked synergism (5- to 6-fold, on average) among cord PBML, whereas this effect was weaker (up to 2-fold) among maternal/adult cells. Prostaglandin E2 (PGE2), at 1.4 x 10(-6) M, inhibited cord and maternal/adult PBML proliferation induced by A23187 (an average 50% inhibition at optimal ionophore concentration). In contrast, PBML cultures stimulated by TPA or by TPA combined with A23187, OKT3 or PHA were virtually insensitive to PGE2-mediated suppression. Our results suggest that PGE2 can down-regulate ionophore-induced, receptor-mediated lymphocyte responses, whereas post-protein kinase C activation events (induced by TPA) are insensitive to PG-mediated inhibition.