Effect of gold compounds on NADPH oxidase system of human neutrophils.

The inhibitory effects of gold compounds on the NADPH oxidase system of human polymorphonuclear leukocytes (PMNs) has been investigated. Auranofin (0.5-4.0 micrograms Au/ml) suppressed the rate of superoxide anion generation as well as the total yield in cells stimulated with phorbol myristate acetate and f-Met-Leu-Phe. This implies that drug action may be occurring at the level of protein kinase C or steps subsequent to this in the signal transduction sequence. Sodium aurothiomalate (1-100 micrograms Au/ml) lacked such activity. Neither gold compound altered the ability of the granule-rich fraction of PMNs to produce oxy radicals whether this fraction was obtained from drug-treated cells or was treated after its isolation. Therefore, in order for auranofin to exhibit its inhibitory effects on the NADPH oxidase system, an intact cell membrane is necessary.