title: Role of Zn2+ and other divalent metal ions in human lymphokine production in vitro.
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 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.
mesh_terms: D000941:Antigens; D002104:Cadmium / Q000494:pharmacology; D002413:Cations, Divalent; D002453:Cell Cycle / Q000187:drug effects; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology; D006801:Humans; D007961:Leukocyte Migration-Inhibitory Factors / Q000096:biosynthesis*; D008222:Lymphokines / Q000096:biosynthesis*; D008670:Metals / Q000494:pharmacology*; D009532:Nickel / Q000494:pharmacology; D010618:Phenanthrolines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D014373:Tuberculin / Q000276:immunology; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000941:Antigens; D002413:Cations, Divalent; D007961:Leukocyte Migration-Inhibitory Factors; D008222:Lymphokines; D008670:Metals; D010618:Phenanthrolines; D010835:Phytohemagglutinins; D014373:Tuberculin; D002104:Cadmium; D003035:Cobalt; D003300:Copper; D009532:Nickel; D015032:Zinc