Role of Zn2+ and Other Divalent Metal Ions in Human Lymphokine Production in Vitro

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Abstract
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 of LIF in a dose-dependent manner by specifically but not by non-specifically stimulated lymphocytes. This paper shows that the 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.