Reactions and reactivity of myeloperoxidase-derived oxidants: Differential biological effects of hypochlorous and hypothiocyanous acids

摘要

Myeloperoxidase (MPO) is recognised to play important roles both in the immune system and during the development of numerous human pathologies. MPO is released by activated neutrophils, monocytes and some tissue macrophages, where it catalyses the conversion of hydrogen peroxide to hypohalous acids (HOX; X = Cl, Br, SCN) in the presence of halide and pseudo-halide ions. The major reactive species produced by MPO under physiological conditions are hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN), with the ratio of these oxidants critically dependent on the concentration of thiocyanate ions (SCN -). The reactivity and selectivity of HOCl and HOSCN for biological targets are markedly different, indicating that SCN - ions have the potential to modulate both the extent and nature of oxidative damage in vivo. This article reviews recent developments in our understanding of the role of SCN - in modulating the formation of MPO-derived oxidants, particularly in respect to the differences in reaction kinetics and targets of HOCl compared to HOSCN and the ability of these two oxidants to induce damage in biological systems.