PROSTAGLANDIN E-2 BIPHASIC CONTROL OF LYMPHOCYTE-PROLIFERATION - INHIBITION BY PICOMOLAR CONCENTRATIONS

Prostaglandins (PGs) have an important physiological role in the modul ation of various cell immune functions, The main sources of PGs during immune responses are monocyte cells. We report here the ability of no n-stimulated macrophages to synthesize prostanoids and show that perit oneal mouse macrophages synthesize PGE(2), PGF(2a) and thromboxane B-2 , spleen macrophages produce PGE(2) and PGF(2a), and in a fresh medium this synthesis reaches a constant basal level in a few hours, We stud ied the kinetics of Con A-induced proliferation of murine splenocytes under the influence of a wide range of PGE(2) concentrations (10(-14)- 10(-7) M). The suppressive effect of PGE(2) decreased when its concent ration was lowered and disappeared at 10(-9) M PGE(2) (this concentrat ion corresponded to the basal level of non-stimulated macrophage synth esis of PGE(2)), Further lowering of the concentration became essentia l for the proliferation process once again, and at picomolar concentra tions PGE(2) caused a suppressive effect comparable with that for 10(- 8) M PGE(2). We also found that PGE(2) significantly inhibited cell pr oliferation when it was added 1 h before the addition of mitogen, as c ompared with simultaneous mitogen addition, The effect was obtained fo r both low (10(-12) M) and high (10(-8) M) PGE(2) concentrations. This phenomenon of PGE(2) biphasic control of lymphocyte proliferation may play an important role in cellular homeostasis, in particular in immu ne cell function regulation. (C) 1997 Federation of European Biochemic al Societies.