Zinc inhibition of respiratory burst in zymosan-stimulated neutrophils: A possible membrane action of zinc.

Abstract

The effect of Zn2+ on the respiratory burst of rat pleural neutrophils was studied. Serum treated zymosan (STZ)-stimulated O2 consumption was inhibited by Zn2+ depending on the Zn2+ concentration and time of cell incubation. Addition of Zn2+ after the stimulation of cells with STZ did not inhibit the O2 consumption. Zn2+ failed to affect the cell viability or the opsonizing process of STZ, indicating that the inhibition of O2 consumption was not due to the direct cytotoxic action of Zn2+ or to the interaction of Zn2+ with STZ. In addition, the activity of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme responsible for the respiratory burst of neutrophils, was not inhibited by Zn2+. These results suggested that Zn2+ may inhibit some process of the activation of NADPH oxidase. Equilimolar Zn2+ 8-hydroxyquinoline complex (Zn-8HQ), which is known to be unable to penetrate the cell membrane, inhibited the O2 consumption more drastically than did Zn2+ alone. 8-Hydroxyquinoline also did not cause significant inhibition of O2 consumption, indicating that the inhibitory effect of Zn2+ is potentiated by complexing with 8-hydroxyquinoline. The inhibition of O2 consumption by Zn2+ was almost completely restored by washing and reincubating the Zn2+-treated cells in Zn2+-free medium. On the other hand, in the cells treated with Zn-8HQ, the same treatment of cell washing and reincubation only partially restored the O2 consumption. These results suggested that Zn2+ may be acting on the cell membrane of neutrophils.