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Published Online: 15 October 2009

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

Publication: Antioxidants & Redox Signaling
Volume 11, Issue Number 11

Abstract

2900Myeloperoxidase (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. Antioxid. Redox Signal. 11, 2899–2937.
I.
Introduction
II.
Properties of MPO
A.
Cellular origin of MPO
B.
MPO gene
1.
Gene structure
2.
Transcriptional activation
3.
Genetic polymorphisms
C.
MPO protein biosynthesis, processing, and structure
D.
Enzymatic properties of MPO
1.
Catalytic mechanisms and redox intermediates of MPO
2.
MPO-derived oxidants
III.
MPO in Health
A.
Microbicidal effects of MPO
B.
Lessons learned from MPO-deficient mice
IV.
MPO in Disease
A.
Properties of MPO in modulating immune responses and inflammation
B.
MPO and cardiovascular diseases
1.
Clinical studies
2.
MPO in endothelial dysfunction
3.
Lipoprotein modification mediated by MPO
4.
Lessons learned from MPO mouse models
C.
MPO and carcinogenesis
D.
MPO and neurodegenerative diseases
E.
MPO and renal diseases
F.
MPO and lung diseases
G.
MPO in other chronic inflammatory diseases
H.
MPO as autoantigen in systemic vasculitis
1.
Clinical observations
2.
In vitro studies involving MPO-ANCA
3.
Lessons learned from MPO-ANCA animal models
V.
MPO Detection in Tissues and Biologic Fluids
VI.
Conclusions

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cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 11Issue Number 11November 2009
Pages: 2899 - 2937
PubMed: 19622015

History

Published in print: November 2009
Published online: 15 October 2009
Published ahead of print: 26 September 2009
Published ahead of production: 21 July 2009
Accepted: 21 July 2009
Revision received: 1 July 2009
Received: 25 February 2009

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Betty S. van der Veen
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Menno P.J. de Winther
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands.
Peter Heeringa
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Notes

Address correspondence to:
Dr. Peter Heeringa
Department of Pathology and Medical Biology
EA11
University Medical Center Groningen
Hanzeplein 1
9713 GZ Groningen
The Netherlands
E-mail: [email protected]

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