Myeloperoxidase in human neutrophil host defence

Abstract

Summary Human neutrophils represent the predominant leucocyte in circulation and the first responder to infection. Concurrent with ingestion of microorganisms, neutrophils activate and assemble the NADPH oxidase at the phagosome, thereby generating superoxide anion and hydrogen peroxide. Concomitantly, granules release their contents into the phagosome, where the antimicrobial proteins and enzymes synergize with oxidants to create an environment toxic to the captured microbe. The most rapid and complete antimicrobial action by human neutrophils against many organisms relies on the combined efforts of the azurophilic granule protein myeloperoxidase and hydrogen peroxide from the NADPH oxidase to oxidize chloride, thereby generating hypochlorous acid and a host of downstream reaction products. Although individual components of the neutrophil antimicrobial response exhibit specific activities in isolation, the situation in the environment of the phagosome is far more complicated, a consequence of multiple and complex interactions among oxidants, proteins and their by‐products. In most cases, the cooperative interactions among the phagosomal contents, both from the host and the microbe, culminate in loss of viability of the ingested organism.

Peptoanaerobacter stomatis Primes Human Neutrophils and Induces Granule Exocytosis

“…It is possible that lactoferrin contributes to P. stomatis killing by inhibiting bacterial growth. Myeloperoxidase, present in the matrix of azurophil granules, is a key enzyme that uses hydrogen peroxide as a substrate to generate the toxic antimicrobial component hypochlorous acid (HOCl) (44). Our data showed that both specific and azurophil granules were efficiently recruited to P. stomatis phagosomes.…”

Neutrophil extracellular traps — the dark side of neutrophils

“…PAD4 may not be necessary for PMA-induced NETs (23), and PMA does not induce a rise in intracellular Ca 2+ that could activate PAD4 (24). MPO, which converts hydrogen peroxide to hypochlorous acid (25), appears to be required for PMA-induced NETosis (26). MPO binds histones and assists elastase during PMA-induced NETosis (8).…”

Homozygous calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency

“…MPO catalyzes the conversion from hydrogen peroxide to hypochlorous acid and is essential for optimal oxygen-dependent antimicrobial activity. 1,2 In the endoplasmic reticulum (ER), glycosylated MPO precursors are chaperoned by the calreticulin (CALR)-calnexin (CNX) cycle. [3][4][5] Both CALR and CNX are lectins that transiently bind to virtually all newly generated glycoproteins (GPs), and their specificity for GPs is mediated by a binding site that recognizes the oligosaccharide Glc 1 Man 9 GlcNAc 2 .…”