Journal of Experimental Medicine, Vol 147, 571-581, Copyright © 1978 by Rockefeller University Press
A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens
RP Daniele, SK Holian and PC Nowell
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.