Role of Zn2+ and other divalent metal ions in human lymphokine production in vitro.

The effects of phenanthroline and of various metal ions on human leucocyte migration inhibitory factor (LIF) production were studied. Previously reported preliminary data showed that phenanthroline, a divalent metal ion chelator, reduced the elaboration o LIF in a dose-dependent manner by specifically but not by non-specifically stimulated lymphocytes. This paper shows that suppression of LIF production caused by phenanthroline could be entirely reversed by Zn2+, Ni2+ and, most effectively, by Co2+. When a battery of divalent cations were tested for direct inhibitory effects on LIF production, Cd2+ and, to a lesser extent, Cu2+ were found to be effective. Again, only specifically stimulated cells were susceptible. This profile of responses resembles greatly that seen in experiments with carboxypeptidases, indicating that a carboxypeptidase-like, probably Zn2+-dependent enzyme is active during antigen-induced lymphokine production. This metalloenzyme may be derived from activated monocytes/macrophages and, like the lymphocyte-activating factor, exerts its activity in the G1 phase of the cell cycle.