Thiotaurine modulates human neutrophil activation.

Abstract

In acute inflammation, neutrophils are activated in response to several agonists generating reactive oxygen species (ROS) by NADPH oxidase-dependent mechanisms. Thiotaurine, a thiosulfonate structurally related to hypotaurine and taurine, is a metabolic product of cystine and contains sulfane sulfur which can play several regulatory roles in biological systems. In the present study, the effects of thiotaurine on human leukocyte activation have been evaluated. Neutrophils were stimulated by phorbol 12-myristate 13-acetate (PMA) or chemotactic peptide (fMLP) and respiratory burst was assessed by luminol enhanced chemiluminescence. Superoxide generation was estimated by measuring cytochrome c reduction. Thiotaurine caused a decrease of the respiratory burst of PMA-stimulated neutrophils in a dose-dependent manner, while fMLP-stimulated cells were slightly affected by thiotaurine. Addition of 100 μM thiotaurine induced 64.4 % inhibition of ROS production by PMA-activated cells, as evaluated by luminol enhanced chemiluminescence. As thiotaurine can release sulfane sulfur producing hydrogen sulfide (H2S) and hypotaurine, the effects of these compounds on leukocyte functional responses were evaluated and compared with those exerted by thiotaurine, which had proved more effective in inhibiting respiratory burst than H2S, hypotaurine and taurine. However, fMLP-induced azurophilic degranulation as analyzed by elastase release was unaffected by thiotaurine up to 5 mM concentration. Compared with fMLP-activated neutrophils, PMA-activated neutrophils were more susceptible to thiotaurine inhibition, suggesting that thiotaurine may interfere with the PKC-dependent pathway of neutrophil activation.