The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease
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The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease. / Davies, Michael Jonathan; Hawkins, Clare Louise.
In: Antioxidants & Redox Signaling, Vol. 32, No. 13, 2020, p. 957-981.Research output: Contribution to journal › Review › peer-review
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TY - JOUR
T1 - The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease
AU - Davies, Michael Jonathan
AU - Hawkins, Clare Louise
PY - 2020
Y1 - 2020
N2 - Significance: The release of myeloperoxidase (MPO) by activated leukocytes is critical in innate immuneresponses. MPO produces hypochlorous acid (HOCl) and other strong oxidants, which kill bacteria and otherinvading 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 andthe molecular targets of HOCl in vivo is an important advance, as typically the involvement of MPO ininflammatory disease has been inferred by its presence, together with the detection of biomarkers of HOCl, inbiological fluids or diseased tissues. This will provide valuable information in regard to the cell types responsiblefor 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 tomitigate tissue damage during chronic inflammation in experimental models, the impact of long-term inhibitionof MPO as a therapeutic strategy for human disease remains uncertain, in light of the potential effects on innateimmunity.Future Directions: The development of more targeted MPO inhibitors or a treatment regimen designed toreduce MPO-associated host tissue damage without compromising pathogen killing by the innate immunesystem is therefore an important future direction. Similarly, a partial MPO inhibition strategy may be sufficientto maintain adequate bacterial activity while decreasing the propagation of inflammatory pathologies.
AB - Significance: The release of myeloperoxidase (MPO) by activated leukocytes is critical in innate immuneresponses. MPO produces hypochlorous acid (HOCl) and other strong oxidants, which kill bacteria and otherinvading 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 andthe molecular targets of HOCl in vivo is an important advance, as typically the involvement of MPO ininflammatory disease has been inferred by its presence, together with the detection of biomarkers of HOCl, inbiological fluids or diseased tissues. This will provide valuable information in regard to the cell types responsiblefor 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 tomitigate tissue damage during chronic inflammation in experimental models, the impact of long-term inhibitionof MPO as a therapeutic strategy for human disease remains uncertain, in light of the potential effects on innateimmunity.Future Directions: The development of more targeted MPO inhibitors or a treatment regimen designed toreduce MPO-associated host tissue damage without compromising pathogen killing by the innate immunesystem is therefore an important future direction. Similarly, a partial MPO inhibition strategy may be sufficientto maintain adequate bacterial activity while decreasing the propagation of inflammatory pathologies.
U2 - 10.1089/ars.2020.8030
DO - 10.1089/ars.2020.8030
M3 - Review
VL - 32
SP - 957
EP - 981
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 13
ER -
ID: 239518514