Neutrophil Myeloperoxidase: Soldier and Statesman

Abstract

Myeloperoxidase (MPO) is a major protein constituent of the primary granules of vertebrate neutrophils. It catalyses the hydrogen peroxide-mediated oxidation of halide ions to hypohalous acids, especially HOCl. These reactive oxygen species can participate in a variety of secondary reactions, leading to modifications of amino acids and many types of biological macromolecules. The classic paradigm views MPO as a component of the phagocyte oxygen-dependent intracellular microbicidal system, and thus an important arm of the effector phase of innate immune responses. However, the limited immunodeficiency associated with lack of MPO in mouse and human models has challenged this paradigm. In this review we examine more recent information on the interaction between MPO, its bioreactive reaction products, and targets within the inflammatory microenvironment. We propose that two assumptions of the current model may require revisiting. First, many important targets of MPO modification are extracellular, rather than present only within the phagolysosome, such as various components of neutrophil extracellular traps. Second, we suggest that the pro-inflammatory pathological role of MPO may be a particular feature of chronic inflammation. In the physiological setting of acute neutrophil-mediated inflammation MPO may also form part of a negative feedback loop which down-regulates inflammation, limits tissue damage, and facilitates the switch from innate to adaptive immunity. This different perspective on this well-studied enzyme may usefully inform further research into its function in health and disease.

Positive Correlation Between Disease Activity Index and Matrix Metalloproteinases Activity in a Rat Model of Colitis

“…The inflammatory infiltrate was observed and histologically confirmed by myeloperoxidase activity (MPO), a marker of inflammatory infiltrate often used in the model of colitis by DSS. MPO is a major enzyme found in the granules of neutrophils, it primarily catalyzes the oxidation of Cl -to hypochlorous acid and its increase is involved in tissue damage (23) . In our study, we observed a high activity of MPO in the DSS group compared to the control group (P<0.001).…”

Effects of inactivated Parapoxvirus ovis on polymorphonuclear leukocyte function and myeloperoxidase activity in horses

“…PMNLs play an important role in the oxygendependent microbicidal system and contain MPO, which is released during their degranulation or lysis (Ponthier et al 2012;Prokopowicz et al 2012). No previous study has shown an interaction between PMNL functions and MPO activity in horses.…”

“…Neutrophils contain MPO, and the enzyme is released during their degranulation or lysis. MPO catalyzes the reaction between H 2 O 2 and chloride ions to form hypochlorous acid, a highly oxidising agent, to kill intracellular microorganisms (Malle et al 2007;Prokopowicz et al 2012).…”

The Contribution of Innate Immunity to the Pathogenesis of ANCA-associated Vasculitis

“…The product generated by MPO is hypochlorous acid (HOCL) and is highly toxic and can react with and oxidize macromolecule such as proteins, DNA and lipids. MPO exert its mechanism during phagocytosis within the phagolysosome, upon degranulation as being part of the released granule content and when present in NETs upon NETosis (Prokopowicz et al 2012). …”

“…Thus, indirectly MPO-ANCA also affects the activity of PR3. It does, however, appear to also be other regulatory mechanisms, such as that HOCL via oxidations not only promote proinflammatory responses but also can inactivate enzymes such as MMP7 and catephsin G as well as MPO itself (Prokopowicz et al 2012). …”