Selenocyanate (SeCN−) acts as an efficient competitive substrate for myeloperoxidase and decreases biological damage induced by hypochlorous acid

The leukocyte-derived enzyme myeloperoxidase (MPO) is a key component of the innate immune response and mediates the killing of pathogens via the generation of the powerful oxidant hypochlorous acid (HOCl). Unintended or excessive formation of this species can however result in damage to host tissues, and this is linked with multiple pathologies associated with acute or chronic inflammation. The active (Compound I) form of MPO is promiscuous and can oxidize multiple alternative anions, in addition to the Cl− used to generate HOCl. These alternative substrates may therefore modulate MPO-mediated HOCl damage. In the current study we examined the hypothesis that selenocyanate (SeCN−), the selenium analogue of thiocyanate (SCN−, a well-established competitive MPO substrate) would inhibit HOCl-mediated damage to human plasma fibronectin (hpFN) or the extracellular matrix laid down by human coronary artery smooth muscle cells. SeCN− modulated HOCl and MPO-mediated damage, in a dose-dependent manner. These data are consistent with SeCN− acting as both a competitive substrate for Compound I of MPO (with IC50 ∼23 μM), and as a direct scavenger of HOCl. Inhibition of protein damage by SeCN− was also detected in the presence of the physiological anions Br−, I− and SCN− at the concentrations typically present in human plasma, consistent with a high affinity of SeCN− for MPO Compound I. In addition, the protective effects of SeCN− and SCN−, as competitive MPO substrates, were additive. Together these data indicate that modest concentrations of SeCN− can, like its sulfur analogue SCN−, act as an effective modulator of inflammation-induced damage.