Myeloperoxidase: Molecular Mechanisms of Action and Their Relevance to Human Health and Disease

Abstract

Myeloperoxidase (MPO) is a heme-containing peroxidase abundantly expressed in neutrophils and to a lesser extent in monocytes. Enzymatically active MPO, together with hydrogen peroxide and chloride, produces the powerful oxidant hypochlorous acid and is a key contributor to the oxygen-dependent microbicidal activity of phagocytes. In addition, excessive generation of MPO-derived oxidants has been linked to tissue damage in many diseases, especially those characterized by acute or chronic inflammation. It has become increasingly clear that MPO exerts effects that are beyond its oxidative properties. These properties of MPO are, in many cases, independent of its catalytic activity and affect various processes involved in cell signaling and cell-cell interactions and are, as such, capable of modulating inflammatory responses. Given these diverse effects, an increased interest has emerged in the role of MPO and its downstream products in a wide range of inflammatory diseases. In this article, our knowledge pertaining to the biologic role of MPO and its downstream effects and mechanisms of action in health and disease is reviewed and discussed.

The Myeloperoxidase-derived Oxidant HOSCN Inhibits Protein Tyrosine Phosphatases and Modulates Cell Signalling via the Mitogen-activated Protein Kinase (MAPK) Pathway in Macrophages

“…However, excessive or misplaced production of these species can result in host tissue damage, with this having been implicated in a wide range of human inflammatory diseases, including cardiovascular disease, rheumatoid arthritis, asthma, cystic fibrosis, some cancers, certain neurodegenerative conditions, kidney disease and inflammatory bowel disease (reviewed in [1][2][3]12]). …”

Intrinsic mutagenic properties of 5-chlorocytosine: A mechanistic connection between chronic inflammation and cancer

“…This type of damage is the result of the infiltration and activation of neutrophil granulocytes (the most abundant leukocyte), which produce myeloperoxidase, an enzyme capable of synthesizing HOCl from hydrogen peroxide and chloride anions ( Fig. 1) (11)(12)(13)(14). The main biomarkers found in cells exposed to HOCl are chlorinated tyrosines (in proteins) and chlorinated nucleobases (in nucleic acids and nucleotide pools) (15,16).…”

The contribution of paraoxonase 1 and myeloperoxidase to HDL-cholesterol functionality

“…Mature MPO is a 150-kDa tetramer composed of two heavy subunits (59-64 kDa) and two light subunits (14 kDa) that are linked together by a disulphide bond [5,59]. Active MPO together with hydrogen peroxide and chloride produces hypochlorous acid which has potent microbicidal actions but also pro-oxidant properties [85]. Additionally, with the neutrophil activation, MPO is released and extracellular MPO has been found in a wide range of acute and chronic inflammatory conditions [62].…”