Inhibition of some functions of polymorphonuclear leukocytes by in vitro zinc

Abstract

In granulocytes isolated by dextran sedimentation from dog blood, the O2 consumption, phagocytosis of yeast particles, and E. coli killing were tested in Tris-guffered saline medium with additions of Zn++, Mg++, and other divalent cations and in the presence or absence of plasma. Zn++ inhibited all three cell functions in a concentration-related manner only in the presence of 1.2 mM Mg++. Without Mg++ in the medium the lower concentrations of Zn++ (17 to 67 muM) were stimulatory; 83 muM Zn++ concentration was inhibitory. A close association was found between the inhibitory effect of Zn++ and the actual content of zinc in the cell: (1) the uptake of zinc from the medium was minimal during the first minute, where no Zn++ effect on cell functions was manifest, (2) when zinc-loaded cells with inhibited activity were washed and reincubated for at least 15 minutes in zinc-free medium, almost 95 per cent of the zinc was washed out and cell activity was normalized. This indicated reversibility of the zinc effect, (3) in the presence of increasing concentrations of autologous plasma in the medium, the effect of zinc was proportionally less pronounced and at the same time uptake of zinc by cells was decreased. Of the six divalent cations studied at 50 muM concentration and in the presence of Mg++, only Zn++ was inhibitory, Se and Co were inactive, and Mn and Cu stimulated O2 consumption of latex-activated granulocytes. We conclude that zinc ions, in the presence of Mg++ in the medium, inhibit various functions of dog peripheral granulocytes and this effect is closely associated with zinc uptake by the cells. The effect is reversible and specific for this metal.