Cited by 333Neutrophil, Myeloperoxidase and Oxidative MechanismsRedox biology and oxidative stressNitric Oxide and Endothelin Effects

The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease

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Davies, Michael J., Hawkins, Clare L.·2020·Antioxidants & Redox Signaling

Abstract

Significance: The release of myeloperoxidase (MPO) by activated leukocytes is critical in innate immune responses. MPO produces hypochlorous acid (HOCl) and other strong oxidants, which kill bacteria and other invading pathogens. However, MPO also drives the development of numerous chronic inflammatory pathologies, including atherosclerosis, neurodegenerative disease, lung disease, arthritis, cancer, and kidney disease, which are globally responsible for significant patient mortality and morbidity. Recent Advances: The development of imaging approaches to precisely identify the localization of MPO and the molecular targets of HOCl in vivo is an important advance, as typically the involvement of MPO in inflammatory disease has been inferred by its presence, together with the detection of biomarkers of HOCl, in biological fluids or diseased tissues. This will provide valuable information in regard to the cell types responsible for releasing MPO in vivo , together with new insight into potential therapeutic opportunities. Critical Issues: Although there is little doubt as to the value of MPO inhibition as a protective strategy to mitigate tissue damage during chronic inflammation in experimental models, the impact of long-term inhibition of MPO as a therapeutic strategy for human disease remains uncertain, in light of the potential effects on innate immunity. Future Directions: The development of more targeted MPO inhibitors or a treatment regimen designed to reduce MPO-associated host tissue damage without compromising pathogen killing by the innate immune system is therefore an important future direction. Similarly, a partial MPO inhibition strategy may be sufficient to maintain adequate bacterial activity while decreasing the propagation of inflammatory pathologies.

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  1. Hawkins CL, Pattison DI, Whiteman M, and Davies MJ. Chlorination and nitration of DNA and nucleic acid components. In: Oxidative Damage to DNA, edited by Evans MD and Cooke MS. Austin, TX: Landes Bioscience and Springer Science, 2006, pp. 14-39.

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Authors
Davies, M. J., & Hawkins, C. L.
Affiliations
University of Copenhagen (DK)
Corresponding author
Hawkins, Clare L.
Venue
Antioxidants & Redox Signaling
Published
2020-03-24
Volume
32
Issue
13
Pages
957-981
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W3003715287
Cited by
332
References
306
Citations by year
2026: 46 · 2025: 56 · 2024: 61 · 2023: 64 · 2022: 54 · 2021: 33 · 2020: 17 · 2019: 1
FWCI
4.13
Type
journal article
Language
en
Open access
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
Novo Nordisk Fonden (NNF17OC0028990, NNF13OC0004294)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
myeloperoxidase, hypochlorous acid, biomolecule modification, chronic inflammation, innate immunity, MPO inhibitors, atherosclerosis, neurodegenerative diseases, lung disease, arthritis, cancer, kidney disease, host tissue damage, bacterial killing
MeSH terms
Animals, Arthritis, Enzyme Inhibitors, Humans, Hypochlorous Acid, Inflammation, Kidney Diseases, Lung Diseases, Peroxidase, Neoplasms, Neurodegenerative Diseases, Atherosclerosis

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