The effect of sodium aurothiomalate on stimulated and non-stimulated migration by human neutrophils: the role of cyclic GMP

Abstract

Preincubation of human neutrophils with aurothiomalate had little effect on random migration or chemotactic migration towards the chemotactic peptide fMLP. However, a strong enhancement of migration was observed when aurothiomalate was present in a concentration gradient; the effect of the drug was chemotactic rather than chemokinetic. Thiomalate also caused a chemotactic enhancement of migration but here a tenfold higher concentration of the drug was required as compared with aurothiomalate. Aurothiomalate caused an increase of cellular cGMP level, and inhibitors of guanylate cyclase inhibited the activating effect of aurothiomalate. Three specific antagonists of cGMP-dependent kinase (G-kinase) strongly inhibited aurothiomalate-induced migration of electroporated neutrophils. The results suggest that stimulation of migration by aurothiomalate is mediated by cGMP and a G-kinase. Monoclonal anti-IL-8 inhibited aurothiomalate-induced stimulation of migration. Though no increased release of IL-8 could be established upon exposure of neutrophils to aurothiomalate, it seems conceivable that the stimulating effect of aurothiomalate is mediated by IL-8.