Neutrophils employ the myeloperoxidase system to generate antimicrobial brominating and chlorinating oxidants during sepsis

The myeloperoxidase system of neutrophils uses hydrogen peroxide and chlori de to generate hypochlorous acid, a potent bactericidal oxidant in vitro. I n a mouse model of polymicrobial sepsis, we observed that mice deficient in myeloperoxidase were more likely than wild-type mice to die from infection . Mass spectrometric analysis of peritoneal inflammatory fluid from septic wild-type mice detected elevated concentrations of 3-chlorotyrosine, a char acteristic end product of the myeloperoxidase system. Levels of 3-chlorotyr osine did not rise in the septic myeloperoxidase-deficient mice. Thus, myel operoxidase seems to protect against sepsis in vivo by producing halogenati ng species. Surprisingly, levels of 3-bromotyrosine also were elevated in p eritoneal fluid from septic wild-type mice and were markedly reduced in per itoneal fluid from septic myeloperoxidase-deficient mice. Furthermore, phys iologic concentrations of bromide modulated the bactericidal effects of mye loperoxidase in vitro. It seems, therefore, that myeloperoxidase can use br omide as well as chloride to produce oxidants in vivo, even though the extr acellular concentration of bromide is at least 1,000-fold lower than that o f chloride. Thus, myeloperoxidase plays an important role in host defense a gainst bacterial pathogens, and bromide might be a previously unsuspected c omponent of this system.