Nigericin, an ionophore that exchanges K+ for H+ across most biologic membranes, reversibly inhibited the proliferative response of human lymphocytes to phytohemagglutinin (PHA). Inhibition occurred at nigericin concentrations of 10(-8) M or greater, and only during the early event of mitogenesis. There was no effect if nigericin was added 24 h or later after the initiation of PHA-stimulated cultures. The effect was not the result of toxicity or impaired mitochondrial respiration. At similar concentrations, nigericin also inhibited lymphocyte responses in mixed lymphocyte cultures and to other mitogens including concanavalin A, pokeweed mitogen, and the calcium ionophore A23187. The findings support the view that one or more transmembranous events, mediated by changes in cation flux and/or membrane potential, are critical in the initial stages of lymphocyte mitogenesis.

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