Differential sensitivity to cAMP among human cord and maternal/adult peripheral lymphocytes discloses differences between PHA- and OKT3-induced activation pathways

Abstract

Previous studies have demonstrated that human cord blood lymphocytes are resistant to the anti-proliferative action of prostaglandin E2 (PGE2) in phytohaemagglutinin (PHA)-induced mitogenesis, whereas the same cells activated by OKT3 are at least as sensitive to PGE2 as the corresponding cells from their mothers or other adults. In the present investigation it was found that: (i) PHA-induced proliferation of cord peripheral blood mononuclear leucocytes (PBML) is less sensitive to inhibition by forskolin--a direct activator of adenylate cyclase (AC)--and dibutyryl cAMP--a permeant cAMP analogue--than the proliferation of the corresponding maternal cells; (ii) OKT3-induced proliferation of cord as well as maternal PBML is highly sensitive to inhibition by forskolin and dibutyryl cAMP; (iii) cord PBML show an overall lower rate of AC activity compared with maternal PBML, in response to PGE2 and other autacoids as well as to receptor-independent stimulation; (iv) cord PBML also display a significantly lower rate of degradation of cAMP through cAMP-phosphodiesterase compared with maternal cells; (v) unbroken cord and maternal PBML show comparable rates of cAMP accumulation after stimulation with PGE2. The results suggest a lower sensitivity to the effect of cAMP in cord compared with maternal/adult lymphocytes in PHA-induced proliferation. Moreover, the data illustrate differences between PHA- and OKT3-mediated activation pathways, as well as differences in cell regulation mechanisms between cord and maternal PBML.