Myeloperoxidase

Myeloperoxidase (MPO) is a heme-containing peroxidase, mainly expressed in neutrophils and, to a lesser extent, in monocytes. ^[1] MPO has a broad bactericidal ability via catalyzing the reaction of chloride with hydrogen peroxide to produce a strong oxidant, hypochlorous acid. ^[1] In a distinct clinical role, MPO is one of the two neutrophil proteins (alongside leukocyte proteinase 3) targeted by autoantibodies known as anti-neutrophil cytoplasmic antibodies in ANCA-associated vasculitis. ^[2]

The MPO-hydrogen-peroxide-halide system uses chloride, the most abundant anion in the human body, as an indispensable constituent to produce the potent microbicide hypochlorous acid within phagosomes. ^[3] The overproduction of MPO-derived oxidants contributes to disease mainly through the oxidation of biomolecules, which promotes inflammation and oxidative stress, and MPO deficiency or MPO inhibitors can attenuate inflammation and tissue injury. ^[1] MPO is presented on the DNA backbone of neutrophil extracellular traps, web-like structures extruded by activated or dying neutrophils that link inflammation, innate immunity, thrombosis, and oxidative stress in cardiovascular disease. ^[4] In ANCA-associated vasculitis the pathogenesis is characterised by a loss of tolerance to the neutrophil enzyme MPO, and MPO-ANCA drives neutrophil activation leading in turn to tissue and organ damage. ^[5]