In vitro modulation of murine natural killer cytotoxicity by zinc.

The in vitro effects of zinc on natural killer (NK) activity of murine spleen cells were studied. The pretreatment of splenocytes with non-toxic concentrations of ZnSO4 induced a decrease of lytic activity against YAC-1 and RDM4 targets. The lytic function of non-activated and poly(I) X poly(C)-activated NK cells was similarly inhibited. When the interaction of effector cells with zinc was studied for 5 min, a significant inhibition of NK lysis was noted, which was maximal after 30 min. Zinc was undoubtedly responsible for the observed effects, since the concurrent addition of both zinc and suitable concentrations of o-phenanthroline, a Zn++ chelating agent, made it possible to maintain a normal level of lysis. Moreover, the pretreatment of spleen cells with increased concentrations of o-phenanthroline also inhibited NK lysis, suggesting that a physiological intracellular zinc content is required to maintain an optimal lytic function of NK cells. Although the lysis was completely suppressed after the addition of 10(-4) M ZnSO4, the frequency of target-binding cells (TBC), which was assumed to represent the first stage of NK-mediated cytolysis, was only partly inhibited. The results are discussed in view of a possible action of zinc on cell membrane functions, enzyme systems, and release of lymphokines.