The role of sulphide in the immune system
Sulphide is gaining attention in the field of biomedical research mainly due to its neuro-modulating properties, which have recently been identified. It is now known that sulphide is produced during metabolism of the amino acid cysteine and has divergent physiological and pathological functions. The EU-funded NHS (Roles of hydrogen sulfide and its metabolites in neutrophil function and redox signaling) project has extended these findings to the neutrophils in the immune system and provided insight into the related molecular mechanisms. Given the promiscuous chemical properties of sulphide, scientists set out to evaluate how it behaves and how it can be detected in physiological samples. They have discovered that biological sulphide in blood and tissues can be found either free at very low levels or attached to various biomolecules. Metalloproteins may be responsible for modulation of sulphide signalling. Project scientists studied the biochemistry of sulphide interactions with neutrophil white blood cells, major players in inflammation. Using lysed human neutrophils and inflamed rat colon extracts, they showed that sulphide could potentially work as an anti-inflammatory through inhibition of myeloperoxidase (MPO) activity. Stimulation of live neutrophils demonstrated the same inhibitory effects. Study of the redox reaction of sulphide with neutrophil-derived oxidants has so far indicated that sulphide inhibits the activity of the neutrophil enzyme MPO even at physiological levels. These findings support the important role of sulphide in MPO-mediated inflammation. Work to delineate the molecular mechanisms of sulphide-regulated cellular signalling indicates protein sulphydration as a major pathway. Using the tumour suppressor PTEN phosphatase as a model enzyme, scientists have discovered that the inhibitory effect of sulphide is mediated through oxidation of the enzyme active-site cysteines. With nitric oxide, a vasorelaxant, the results showed that crosstalk produced three main products. Using in vitro and in vivo models indicated their totally different biochemical properties. NHS work provides important insight into the role and mechanism of sulphide on neutrophil function. The obtained results should significantly advance our understanding of how drugs targeting the complex behaviour of hydrogen sulphide may be effective.
Keywords
Sulphide, immune system, anti-inflammatory, neutrophil, nitric oxide
