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Neutrophil Myeloperoxidase: Soldier and Statesman

  • Review
  • Published:
Archivum Immunologiae et Therapiae Experimentalis Aims and scope

An Erratum to this article was published on 26 November 2014

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.

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Abbreviations

ANCA:

Anti-neutrophil cytoplasmic autoantibodies

DC:

Dendritic cell

ER:

Endoplasmic reticulum

HDL:

High density lipoprotein

HOCl:

Hypochlorous acid

HOBr:

Hypobromous acid

H2O2 :

Hydrogen peroxide

LDL:

Low density lipoprotein

MMP:

Matrix metalloproteinase

MPO:

Myeloperoxidase

NADPH:

Nicotinamide adenine dinucleotide phosphate

NET:

Neutrophil extracellular trap

PAMP:

Pathogen-associated molecular pattern

PRR:

Pattern recognition receptor

TLRs:

Toll-like receptors

SVV:

Small-vessel vasculitides

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Acknowledgments

Authors thank Dr Rafał Biedroń for assistance in the preparation of this manuscript for publication. Zofia Prokopowicz was supported by a MRC studentship. Benjamin Chain is supported by a grant from Ovarian Cancer Action. Janusz Marcinkiewicz is supported by a grant from the Jagiellonian University Medical College (Grant no. K/ZDS/001008 and Grant no. K/PBW/000643).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Division of Infection and Immunity, Department of Immunology, UCL, London, UK

    Zofia Prokopowicz, David R. Katz & Benjamin M. Chain

  2. Department of Immunology, Jagiellonian University Medical College, 18 Czysta, 31-121, Kraków, Poland

    Janusz Marcinkiewicz

Authors
  1. Zofia Prokopowicz
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  2. Janusz Marcinkiewicz
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  3. David R. Katz
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  4. Benjamin M. Chain
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Corresponding author

Correspondence to Janusz Marcinkiewicz.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00005-014-0321-y.

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Prokopowicz, Z., Marcinkiewicz, J., Katz, D.R. et al. Neutrophil Myeloperoxidase: Soldier and Statesman. Arch. Immunol. Ther. Exp. 60, 43–54 (2012). https://doi.org/10.1007/s00005-011-0156-8

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  • DOI: https://doi.org/10.1007/s00005-011-0156-8

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