Differential effects of the calcium ionophore A23187 and the phorbol ester PMA on lymphocyte proliferation

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Abstract
The effects of the phorbol ester, phorbol-12-myristate-13-acetate (PMA), and of the calcium ionophore A23187 on DNA synthesis in murine quiescent and mitogen-stimulated lymphocytes have been examined. Neither PMA nor A23187 had any mitogen effect on their own on quiescent lymphocytes. However, stimulation of cells sequentially with A23187 and then PMA resulted in a proliferative response in proportion to the duration of the exposure to A23187, and the sustained simultaneous presence of both agents was necessary for maximum proliferation. On the other hand, while short incubations with A23187 potentiated mitogen-induced DNA synthesis, prolonged exposure inhibited it. Furthermore, on lymphocytes stimulated with two T cell mitogens, the effects of A23187 and PMA depended on the proliferation-inducing mitogens and the responsiveness level induced by them. Therefore, while PMA and short pretreatments with A23187 had no effect on high intensity mitogenic responses, low intensity responses were significantly enhanced. These results demonstrate differential effects of A23187 and PMA on DNA synthesis that should be useful in studies on the mechanisms of activation of lymphocyte proliferation.