Affinage

MPO

Myeloperoxidase · UniProt P05164

Round 2 corrected
Length
745 aa
Mass
83.9 kDa
Annotated
2026-04-28
130 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Myeloperoxidase (MPO) is a heme-containing heterotetrameric peroxidase stored in neutrophil azurophilic granules that generates hypohalous acids (HOCl, HOBr, HOSCN) from halides and thiocyanate using H₂O₂, with thiocyanate as the kinetically preferred substrate (SCN⁻ >> I⁻ > Br⁻ >> Cl⁻), and also catalytically consumes nitric oxide to modulate vascular NO bioavailability (PMID:9359420, PMID:9922160, PMID:11090610, PMID:12089442). During NETosis, MPO forms a granule-membrane complex with neutrophil elastase (NE); ROS-triggered dissociation releases and activates NE, which degrades F-actin and translocates to the nucleus to decondense chromatin, after which MPO synergizes non-enzymatically to complete chromatin decondensation—making MPO essential for PMA-induced but dispensable for ionophore-induced NET formation (PMID:20974816, PMID:20974672, PMID:25066128, PMID:28574339). MPO also drives vascular inflammation by activating endothelial µ-calpain via denitrosylation, suppressing eNOS phosphorylation through PP2A, and by generating oxidized LDL species recognized by the scavenger receptor CD36 to promote foam cell formation and atherosclerotic plaque instability (PMID:29507101, PMID:10772654, PMID:36375379). A homozygous loss-of-function MPO mutation (p.Arg590Leu) that abolishes heme binding is associated with generalized pustular psoriasis and defective NETosis (PMID:36585391).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Determination of the first MPO crystal structure revealed the heterotetrameric architecture, covalent heme attachment, and catalytic residues (proximal His336, distal His95/Arg239), establishing the structural framework for understanding halide oxidation.

    Evidence X-ray crystallography at 3 Å of canine MPO with multiple isomorphous replacement

    PMID:1320128

    Open questions at the time
    • Covalent heme linkages only tentatively assigned at this resolution
    • Human MPO structure not yet determined
    • No halide-binding site directly visualized
  2. 1994 High

    Identification of a myeloid-specific upstream enhancer and proximal promoter elements established the transcriptional regulatory framework for lineage-restricted MPO expression.

    Evidence DNase I hypersensitivity mapping and reporter assays in myeloid vs. lymphoid cell lines; DNase I footprinting and site-directed mutagenesis of promoter elements

    PMID:8182931 PMID:8683986

    Open questions at the time
    • Trans-acting factors binding DP1–DP7 elements not identified
    • Chromatin context in primary myeloid progenitors not assessed
  3. 1997 High

    Kinetic characterization revealed thiocyanate as MPO's most favored physiological substrate over chloride and bromide, reframing MPO as a hypothiocyanite-producing enzyme alongside its HOCl-generating role, while ceruloplasmin was identified as a physiological inhibitor of MPO activity.

    Evidence In vitro enzyme kinetics with varied substrate concentrations; MPO-affinity chromatography and reciprocal binding assays with purified ceruloplasmin

    PMID:9097926 PMID:9359420

    Open questions at the time
    • In vivo relative contributions of HOSCN vs. HOCl not quantified
    • Structural basis of ceruloplasmin–MPO interaction unknown
  4. 1998 High

    Stopped-flow transient kinetics defined absolute rate constants for compound I reduction by each halide and SCN⁻, revealing a catalytic residue with pKa ~4.6 required for halide oxidation and establishing that SCN⁻ most effectively shifts MPO from the peroxidatic to the halogenation cycle.

    Evidence Sequential mixing stopped-flow spectroscopy with compound I/II intermediates

    PMID:9922160

    Open questions at the time
    • Identity of the pKa ~4.6 residue not assigned
    • Phagosomal pH dynamics not integrated
  5. 2000 High

    High-resolution human MPO structure resolved the three covalent heme linkages (Glu242, Asp94 ester bonds; Met243 sulfonium) and identified the distal halide-binding site, while parallel work established MPO as a catalytic NO sink and showed MPO-oxidized LDL drives CD36-dependent foam cell formation.

    Evidence 1.8 Å X-ray crystallography of native and bromide-soaked crystals; stopped-flow NO consumption kinetics; CD36-transfected cells, CD36-null macrophages, and blocking antibodies

    PMID:10766826 PMID:10772654 PMID:11090610

    Open questions at the time
    • In vivo NO consumption kinetics at inflammatory sites not measured
    • Structural basis of MPO–LDL interaction unresolved
    • Compound I–halide ternary complex not crystallized
  6. 2002 High

    MPO-deficient mice demonstrated that MPO catalytically consumes NO in vivo to impair endothelium-dependent vasodilation during inflammation, while granule protease-deficient mice showed that neutrophil proteases (not MPO-derived oxidants alone) are the primary bactericidal effectors, and promoter studies defined P1 as the physiologically relevant transcription start site.

    Evidence MPO-KO and protease-KO mouse infection/vascular relaxation models; primer extension and RT-PCR in differentiating myeloid cells

    PMID:11907569 PMID:12040446 PMID:12089442

    Open questions at the time
    • Relative contribution of HOCl vs. chloramines to microbial killing in vivo unresolved
    • Mechanism of MPO subendothelial transcytosis not determined
  7. 2003 High

    Surface-expressed MPO was shown to be required for anti-MPO ANCA-mediated neutrophil activation, linking MPO to ANCA-associated vasculitis pathogenesis.

    Evidence Superoxide production assays in neutrophils from MPO-deficient donors stimulated with anti-MPO antibodies

    PMID:12773517

    Open questions at the time
    • Mechanism of MPO surface translocation not defined
    • Whether surface MPO retains enzymatic activity during ANCA engagement unknown
  8. 2010 High

    MPO was established as essential for PMA-induced NETosis through a non-enzymatic synergy with neutrophil elastase in chromatin decondensation, with NE requiring prior MPO-dependent release from azurophilic granules and nuclear translocation to degrade histones.

    Evidence NE-KO mice with pulmonary infection; neutrophils from completely MPO-deficient human donors; granule fractionation and nuclear translocation imaging; NET quantification and Candida killing assays

    PMID:20974672 PMID:20974816

    Open questions at the time
    • Molecular basis of MPO's non-enzymatic chromatin decondensation activity unknown
    • Whether MPO directly binds chromatin or histones not tested
  9. 2014 High

    Discovery that MPO and NE form a membrane-associated complex in azurophilic granules that acts as a ROS-sensing scaffold resolved how oxidative signals trigger NE release: ROS dissociates NE from MPO, enabling NE to degrade F-actin and halt actin dynamics before nuclear translocation.

    Evidence Co-immunoprecipitation; biochemical fractionation; actin dynamics assays; MPO inhibitors; NE activity assays

    PMID:25066128

    Open questions at the time
    • Stoichiometry and structural basis of the MPO–NE complex not determined
    • ROS species responsible for complex dissociation not identified
  10. 2016 High

    Reconstitution of MPO biosynthesis in a non-myeloid cell line demonstrated that Cys319 is required not only for the inter-molecular disulfide bond forming the heterotetramer but also for correct glycosylation and entry into the endocytic processing pathway.

    Evidence Stable transfection of MPO into T47D cells; Cys319 site-directed mutagenesis; glycosylation analysis and endocytic pathway microscopy

    PMID:26890638

    Open questions at the time
    • Chaperones and proteases mediating pro-domain removal not identified
    • Structural basis of Cys319-dependent glycosylation control unclear
  11. 2017 High

    Systematic dissection of NETosis stimuli confirmed two distinct pathways: a PKC/ROS/MPO/NE-dependent pathway (PMA, Candida, Streptococcus) and an MPO/NADPH oxidase-independent calcium pathway (ionophores), clarifying the stimulus-dependent requirement for MPO.

    Evidence Pharmacological inhibitor panel plus neutrophils from CGD and MPO-deficient patients across multiple stimuli

    PMID:28574339

    Open questions at the time
    • Calcium-dependent NETosis effectors downstream of ionophore not identified
    • Whether mixed pathways operate simultaneously in vivo unknown
  12. 2018 High

    MPO was shown to activate endothelial µ-calpain (but not m-calpain) through denitrosylation, establishing a signaling cascade (µ-calpain → PP2A → AMPK/eNOS dephosphorylation → VCAM-1 upregulation) that explains how MPO promotes vascular inflammation beyond oxidant generation.

    Evidence Endothelial cell stimulation; calpain isoform-specific assays; µ-calpain-deficient mice; phosphorylation western blots; leukocyte adhesion assay

    PMID:29507101

    Open questions at the time
    • Direct denitrosylation of µ-calpain not demonstrated biochemically with purified proteins
    • Whether this pathway operates in human vasculature in vivo not confirmed
  13. 2022 High

    Multiple 2022 studies consolidated MPO's pathological roles: pharmacological MPO inhibition stabilized atherosclerotic plaque in vivo, a homozygous loss-of-function mutation (Arg590Leu) abolishing heme binding was linked to generalized pustular psoriasis with defective NETosis, and MPO inhibition attenuated acute lung injury via the µ-calpain/β-catenin pathway.

    Evidence Tandem Stenosis mouse model with AZM198 and molecular MRI; patient mutation analysis with structural prediction and in vitro activity assay; rat ALI model with verdiperstat and junction protein analysis

    PMID:35461824 PMID:36375379 PMID:36585391

    Open questions at the time
    • Clinical efficacy of MPO inhibitors in human cardiovascular or pulmonary disease not demonstrated
    • Mechanistic link between MPO deficiency and pustular psoriasis pathogenesis beyond NETosis not explored
    • β-catenin signaling downstream of µ-calpain not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the non-enzymatic MPO–chromatin interaction during NETosis, the identity of the ROS species dissociating the MPO–NE granule complex, the in vivo relative contributions of HOCl vs. HOSCN vs. chloramines to antimicrobial defense, and whether therapeutic MPO inhibition translates to clinical benefit in cardiovascular and inflammatory diseases.
  • No structural model of MPO bound to chromatin or NE exists
  • In vivo pharmacokinetics of MPO-generated oxidants within the phagosome remain modeled rather than measured
  • Clinical trials of MPO inhibitors in atherosclerosis or ANCA vasculitis are ongoing but lack definitive outcomes

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 8 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 2 GO:0031410 cytoplasmic vesicle 2 GO:0005764 lysosome 1
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 4
Partners
CAPN1CD36CPELANE
Complex memberships
MPO-NE azurophilic granule membrane complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 X-ray crystal structure of canine myeloperoxidase at 3 Å resolution revealed a heterotetrameric enzyme (two heavy and two light chains linked by a disulfide bridge), with a covalently bound heme, proximal His336 ligand to heme iron, distal His95 and Arg239 as catalytic residues, a calcium binding site, and covalent linkage to heme tentatively at Glu242. X-ray crystallography (multiple isomorphous replacement, crystallographic refinement) Journal of molecular biology High 1320128
2000 X-ray crystal structure of human MPO at 1.8 Å confirmed covalent heme attachment via two ester linkages (Glu242 and Asp94 to modified pyrrole methyl groups on rings A and C) and a sulfonium ion linkage (Met243 to vinyl group on pyrrole ring A). Halide-binding sites were characterized: a native chloride ion near the proximal His336 helix, and a bromide-binding site in the distal heme cavity near His95 that competes with H2O2 and may serve as the halide substrate-binding site in compound I. X-ray crystallography at 1.8 Å (native and bromide-soaked crystals) The Journal of biological chemistry High 10766826
1997 Kinetic studies established that thiocyanate is by far the most favored substrate for MPO over chloride and bromide (relative specificity constants Cl:Br:SCN = 1:60:730). At physiological concentrations of thiocyanate and chloride, MPO produces hypothiocyanite alongside HOCl, demonstrating thiocyanate as a major physiological substrate. In vitro enzyme kinetics (H2O2 consumption assay at varied substrate concentrations) The Biochemical journal High 9359420
1998 Stopped-flow transient kinetics revealed second-order rate constants for two-electron reduction of MPO compound I by halides and thiocyanate at pH 7: Cl⁻ (2.5×10⁴ M⁻¹s⁻¹), Br⁻ (1.1×10⁶ M⁻¹s⁻¹), I⁻ (7.2×10⁶ M⁻¹s⁻¹), SCN⁻ (9.6×10⁶ M⁻¹s⁻¹). A catalytic residue with pKa ~4.6 must be protonated for optimal halide oxidation. SCN⁻ most effectively shifts MPO from the peroxidatic to the halogenation cycle. Sequential mixing stopped-flow transient kinetics; steady-state spectral and kinetic measurements Biochemistry High 9922160
2000 MPO catalytically consumes nitric oxide (NO) as a substrate via its compound I and compound II intermediates in a H2O2-dependent manner, independent of chloride. Stopped-flow kinetics showed NO dramatically influences compound II steady-state levels, identifying peroxidases including MPO as a catalytic sink for NO at inflammation sites. Stopped-flow kinetics; steady-state NO consumption assay; in vitro enzyme assay with superoxide-generating system The Journal of biological chemistry High 11090610
2000 CD36 was identified as the major macrophage scavenger receptor for LDL modified by the MPO-H2O2-NO2⁻ system (NO2-LDL). MPO-dependent LDL modification generates a high-affinity CD36 ligand leading to foam cell formation; lipid oxidation products of phosphatidylcholine serve as the CD36-recognized moieties. Stable transfection of CD36; CD36-specific blocking mAbs; CD36-null macrophages; cholesterol loading and binding assays The Journal of clinical investigation High 10772654
2002 MPO localizes in and around vascular endothelial cells following leukocyte degranulation during acute endotoxemia, where it catalytically consumes NO via substrate radicals, impairing endothelium-dependent relaxation. MPO-deficient mice were resistant to this vascular dysfunction, establishing MPO as a vascular NO oxidase modulating NO bioavailability during inflammation. Rodent model of acute endotoxemia; MPO-deficient mice; vascular relaxation assays; direct localization studies Science High 12089442
2002 K⁺ flux into the neutrophil phagosome raises ionic strength and releases cationic granule proteins (elastase, cathepsin G) from anionic proteoglycan matrix; MPO-catalyzed halogenation contributes to the phagosomal oxidative environment. Mice deficient in granule proteases (but with intact superoxide/MPO activity) cannot resist staphylococcal/candidal infections, showing proteases are primary bactericidal effectors with MPO providing the oxidative context. Protease-deficient KO mice; infection models; ion flux measurements; morphological analysis Nature High 11907569
2006 Kinetic modeling of the neutrophil phagosome showed that MPO (present at millimolar concentrations) rapidly converts most superoxide to compound III, that superoxide is essential to recycle compound III and maintain MPO activity, and that MPO efficiently produces HOCl when chloride is adequate. Most HOCl reacts with granule proteins before reaching bacteria, and chloramine products may be the antimicrobial effectors. Kinetic mathematical modeling using known rate constants; estimated phagosomal concentrations The Journal of biological chemistry Medium 17074761
2010 Upon neutrophil activation, neutrophil elastase (NE) escapes azurophilic granules and translocates to the nucleus where it degrades specific histones, promoting chromatin decondensation for NET formation. MPO then synergizes with NE to drive further chromatin decondensation independently of its enzymatic activity. NE-knockout mice fail to form NETs in a pulmonary Klebsiella pneumoniae model. NE-KO mice; pulmonary infection model; granule fractionation; nuclear translocation imaging; inhibitor studies; NET quantification The Journal of cell biology High 20974816
2010 Neutrophils from completely MPO-deficient donors fail to form NETs, establishing MPO as required for NET formation. Partial MPO deficiency allows NET formation; pharmacological MPO inhibition only delays/reduces NETs. MPO acts cell-autonomously (extracellular MPO products cannot rescue NET formation). NET-dependent killing of Candida albicans is compromised in MPO-deficient neutrophils. Neutrophils from MPO-deficient patients; pharmacological MPO inhibition; NET quantification; Candida killing assay Blood High 20974672
2010 Human neutrophil MPO catalyzes biodegradation of single-walled carbon nanotubes via hypochlorite and reactive radical intermediates, both in vitro and in intact neutrophils. Molecular modeling indicated basic amino acids of MPO interact with carboxyls on nanotubes to position them near the catalytic site. Biodegraded nanotubes do not induce pulmonary inflammation in mice. In vitro MPO enzymatic assay; cell-based degradation in neutrophils and macrophages; molecular modeling; mouse aspiration model Nature nanotechnology High 20364135
2011 MPO bound to NETs retains enzymatic peroxidase activity (~30% of total cellular MPO released with majority NET-bound). NET-associated MPO mediates H2O2-dependent killing of Staphylococcus aureus, demonstrating that MPO on NETs can contribute to extracellular antimicrobial activity. PMA-stimulated NET formation; peroxidase activity assay on NETs; MPO inhibitor; S. aureus killing assay with DNase-released NETs Journal of leukocyte biology High 22131345
2012 Requirements for NADPH oxidase and MPO in NET formation are stimulus-dependent: PMA and bacterial stimuli require NADPH oxidase; MPO is required for efficient PMA-induced NETs but dispensable for bacterium-induced NETs. Ionomycin (calcium ionophore) induces NETs independently of both NADPH oxidase and MPO. NADPH oxidase and MPO inhibitors; cells from MPO-deficient donor; multiple stimuli (PMA, bacteria, ionomycin); NET quantification Journal of leukocyte biology High 22802447
2014 MPO forms a membrane-associated complex in azurophilic granules with NE that prevents NE release. ROS triggers MPO-dependent dissociation of NE from this complex into the cytosol and activates NE proteolytic activity. In the cytosol, NE binds and degrades F-actin to arrest actin dynamics before translocating to the nucleus during NETosis. This complex functions as an oxidative signaling scaffold. Biochemical fractionation; co-immunoprecipitation; actin dynamics assays; MPO inhibitors; NE activity assays; NET formation imaging Cell reports High 25066128
2017 Different NETosis stimuli engage distinct signaling pathways: PMA, C. albicans, and Group B Streptococcus use a PKC/ROS/MPO/NE-dependent pathway, whereas calcium ionophores (A23187, nigericin) require an alternative pathway independent of MPO and NADPH oxidase. All NET types are proteolytically active and kill bacteria. Pharmacological inhibitors (PKC, calcium, ROS, MPO, NE); neutrophils from chronic granulomatous disease and MPO-deficient patients; multiple stimuli; bacterial killing assay eLife High 28574339
2004 Enzymatically active MPO and its oxidation products (chlorotyrosine) are present in human brain neurons (hippocampal granule and pyramidal neurons) and activated microglia. MPO expression is increased in Alzheimer's disease brain tissue particularly in neurons and amyloid plaques. Several neuronal cell lines express MPO mRNA and protein, revealing unexpected neuronal expression of MPO. Immunohistochemistry; enzymatic activity assay; mass spectrometric detection of chlorotyrosine; RT-PCR; neuronal cell line analysis Journal of neurochemistry High 15255951
1997 Ceruloplasmin physically binds MPO and inhibits its peroxidase activity in a concentration-dependent manner. This interaction was demonstrated by MPO-affinity chromatography retaining ceruloplasmin from plasma, selective binding to MPO-coated plates (blockable by soluble MPO), and reciprocal binding of MPO to ceruloplasmin-coated plates (blockable by ceruloplasmin). C3 also binds MPO but does not inhibit its peroxidase activity. MPO-affinity chromatography; N-terminal amino acid sequencing; ELISA binding assays; peroxidase activity inhibition assay Clinical and experimental immunology High 9097926
2003 Expression of MPO on the neutrophil surface is required for neutrophil activation by anti-MPO antibodies (ANCA). MPO-deficient neutrophils (completely and partially) showed no superoxide anion production in response to monoclonal anti-MPO or MPO-ANCA IgG, despite normal responses to other stimuli. Mutations causing deficiency were characterized at the molecular level. Neutrophils from MPO-deficient donors; superoxide anion production assay; immunocytochemistry; immunoblotting; mutation sequencing Journal of leukocyte biology High 12773517
2018 MPO activates µ-calpain (but not m-calpain) in endothelial cells through denitrosylation of the µ-calpain C-terminus domain. Activated µ-calpain upregulates PP2A expression, which dephosphorylates AMPK (Thr172) and eNOS (Ser1177), leading to increased VCAM-1 and leukocyte adhesion. µ-Calpain-deficient mice showed reduced leukocyte adhesion in response to MPO, placing calpain as a novel downstream signaling target in MPO-induced endothelial dysfunction. Endothelial cell stimulation with MPO; calpain isoform-specific assays; pharmacological calpain inhibition; PP2A/AMPK/eNOS phosphorylation western blots; µ-calpain-deficient mice; leukocyte adhesion assay Hypertension High 29507101
2016 T47D breast cancer cells stably transfected with MPO replicate all post-ER processing steps for mature MPO heterotetramer formation, including proteolytic pro-domain removal, heavy/light chain separation, and inter-molecular disulfide bond formation. MPO traffics to lysosomes. Cys319 (which forms the inter-molecular disulfide bond) is also required for events preceding disulfide bonding: its mutation alters glycosylation, catalytic activity, and blocks entry into the endocytic pathway where proteolytic processing occurs. Stable transfection of MPO into T47D cells; site-directed mutagenesis of Cys319; immunofluorescence microscopy; glycosylation analysis; catalytic activity assay; endocytic pathway analysis PloS one High 26890638
1996 The human MPO promoter contains seven discrete nuclear protein binding sites (DP1–DP7) within the proximal 600 bp of 5'-flanking DNA, identified by DNase I footprinting and gel shift analysis. These sites show tissue-specific and maturation-specific differences in nuclear protein binding. Mutation of DP7 stimulates MPO promoter activity, while mutation of any of DP1–DP6 reduces activity, establishing them as positive cis-regulatory elements. DNase I footprinting; gel shift assays; promoter-reporter transfection with site-directed mutations Leukemia High 8683986
1994 A myeloid-lineage-specific enhancer for the murine MPO gene was identified 3.2–3.4 kb upstream, marked by a DNase I hypersensitive site. A 301 bp fragment encompassing this site has strong enhancer activity in MPO-expressing myeloid cells (WEHI 3BD+) but is inactive in lymphoid cells, requiring the complete 301 bp fragment for maximal activity. DNase I hypersensitivity mapping; transient transfection reporter assay in myeloid vs. lymphoid cell lines Leukemia High 8182931
2002 The human MPO gene is transcribed in vivo primarily from the P1 promoter (~bp +1), with two additional non-canonical transcription initiation sites at P2 (~bp -310) and P3 (~bp -920). Transcription from P1 produces full-length coding transcripts and shows the expected downregulation upon myeloid differentiation. P2 and P3 transcripts do not downregulate upon TPA-induced macrophage differentiation, are non-tissue-specific, frequently terminate prematurely, and do not contribute to physiologic MPO expression. Primer extension; RT-PCR; Northern blot analysis of myeloid cell lines before and after differentiation induction Leukemia High 12040446
2022 MPO inhibition with the suicide inhibitor AZM198 stabilizes pre-existing unstable atherosclerotic plaque in the Tandem Stenosis mouse model, increasing fibrous cap thickness indicative of plaque stabilization, without altering cellular content (Ly6B.2+ or CD68+ cells) or MPO protein levels. In vivo molecular MRI showed elevated arterial MPO activity precedes unstable plaque formation. Tandem Stenosis mouse model; pharmacological MPO inhibition (AZM198); in vivo molecular MRI of MPO activity; histological analysis Redox biology High 36375379
2022 A homozygous missense mutation c.1769G>T (p.Arg590Leu) in MPO abolishes heme binding (structural analysis) and completely eliminates myeloperoxidase enzymatic activity in vitro. The mutant protein is stably expressed in culture but shows markedly reduced expression in patient skin in vivo, and is associated with generalized pustular psoriasis (GPP). Reduced NETosis (sparse NET formation in pustules) was observed in patient skin. Structural analysis (in silico heme binding prediction); in vitro myeloperoxidase activity assay in cultured cells; immunohistochemistry (anti-MPO and anti-citrullinated histone H3) The Journal of dermatology High 36585391
2022 MPO-oxidized LDLs (Mox-LDLs) drive macrophage foam cell formation and increase intracellular ROS, but also stimulate endothelial cells to produce resolvin D1 (RvD1), a specialized pro-resolving mediator that reduces neutrophil/monocyte recruitment and promotes efferocytosis. Mox-LDLs thus exert a dual effect on inflammation through MPO-dependent LDL oxidation. In vitro cell-based assays with Mox-LDLs and macrophages/endothelial cells; RvD1 measurement Antioxidants Medium 35624738
2022 MPO inhibition with verdiperstat attenuates LPS-induced acute lung injury in rats via the MPO/µ-calpain/β-catenin signaling pathway: MPO inhibition reduces µ-calpain activation, decreases nuclear β-catenin translocation, and restores VE-cadherin and claudin-5 levels, strengthening endothelial barrier function. LPS-induced two-hit rat ALI model; verdiperstat (MPO inhibitor) treatment; western blotting of µ-calpain cleavage, β-catenin localization, VE-cadherin, claudin-5; in vitro HPMEC model European journal of pharmacology Medium 35461824

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Neutrophil elastase and myeloperoxidase regulate the formation of neutrophil extracellular traps. The Journal of cell biology 1696 20974816
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2002 Killing activity of neutrophils is mediated through activation of proteases by K+ flux. Nature 851 11907569
2003 Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 785 12952835
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2017 Diverse stimuli engage different neutrophil extracellular trap pathways. eLife 640 28574339
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2010 Myeloperoxidase is required for neutrophil extracellular trap formation: implications for innate immunity. Blood 602 20974672
2014 A myeloperoxidase-containing complex regulates neutrophil elastase release and actin dynamics during NETosis. Cell reports 590 25066128
2002 Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science (New York, N.Y.) 556 12089442
2012 Myeloperoxidase: a front-line defender against phagocytosed microorganisms. Journal of leukocyte biology 491 23066164
2010 Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation. Nature nanotechnology 484 20364135
2006 Modeling the reactions of superoxide and myeloperoxidase in the neutrophil phagosome: implications for microbial killing. The Journal of biological chemistry 460 17074761
2013 Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab. Journal of the American College of Cardiology 431 24291281
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2000 Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. The Journal of clinical investigation 375 10772654
2012 Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus. Journal of leukocyte biology 353 22802447
2005 Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Journal of proteome research 350 16335952
1997 Thiocyanate and chloride as competing substrates for myeloperoxidase. The Biochemical journal 335 9359420
2000 Nitric oxide is a physiological substrate for mammalian peroxidases. The Journal of biological chemistry 332 11090610
2000 X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution. The Journal of biological chemistry 287 10766826
2013 C5a receptor (CD88) blockade protects against MPO-ANCA GN. Journal of the American Society of Nephrology : JASN 277 24179165
2011 Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide. Journal of leukocyte biology 272 22131345
2004 Neuronal expression of myeloperoxidase is increased in Alzheimer's disease. Journal of neurochemistry 269 15255951
2005 CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis. Genetics in medicine : official journal of the American College of Medical Genetics 263 15714076
1992 X-ray crystal structure of canine myeloperoxidase at 3 A resolution. Journal of molecular biology 253 1320128
1998 Reaction of myeloperoxidase compound I with chloride, bromide, iodide, and thiocyanate. Biochemistry 239 9922160
2020 Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds. Frontiers in physiology 202 32508671
2004 Genetic polymorphisms of MPO, COMT, MnSOD, NQO1, interactions with environmental exposures and bladder cancer risk. Carcinogenesis 165 14729580
2009 Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy. Journal of clinical periodontology 123 19995403
2002 Role of NQO1, MPO and CYP2E1 genetic polymorphisms in the susceptibility to childhood acute lymphoblastic leukemia. International journal of cancer 119 11774269
2012 The expression of genes encoding for COX-2, MPO, iNOS, and sPLA2-IIA in patients with recurrent depressive disorder. Journal of affective disorders 112 22331023
1997 Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin? Clinical and experimental immunology 112 9097926
2008 MPO-ANCA induces IL-17 production by activated neutrophils in vitro via classical complement pathway-dependent manner. Journal of autoimmunity 89 18501296
2016 Peptidylarginine Deiminase Inhibitor Suppresses Neutrophil Extracellular Trap Formation and MPO-ANCA Production. Frontiers in immunology 88 27375623
2015 NADPH oxidase, MPO, NE, ERK1/2, p38 MAPK and Ca2+ influx are essential for Cryptosporidium parvum-induced NET formation. Developmental and comparative immunology 88 26026247
2005 NQO1, MPO, and the risk of lung cancer: a HuGE review. Genetics in medicine : official journal of the American College of Medical Genetics 86 16170238
1996 T cell responses to myeloperoxidase (MPO) and proteinase 3 (PR3) in patients with systemic vasculitis. Clinical and experimental immunology 77 8565308
2012 Fibrosis in Atrial Fibrillation - Role of Reactive Species and MPO. Frontiers in physiology 76 22723783
2021 Neutrophil Extracellular Traps: A Potential Therapeutic Target in MPO-ANCA Associated Vasculitis? Frontiers in immunology 68 33790907
2021 The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication. Antioxidants (Basel, Switzerland) 60 33916434
2010 Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis. Kidney international 59 20844472
2008 NQO1, MPO, CYP2E1, GSTT1 and GSTM1 polymorphisms and biological effects of benzene exposure--a literature review. Toxicology letters 59 18848868
2005 CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung. Carcinogenesis 59 16195240
2021 ELISA detection of MPO-DNA complexes in human plasma is error-prone and yields limited information on neutrophil extracellular traps formed in vivo. PloS one 56 33886636
2000 Serum ECP and MPO are increased during exacerbations of chronic bronchitis with airway obstruction. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 49 10917466
2015 Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies. Scientific reports 48 26149790
2003 Expression of myeloperoxidase (MPO) by neutrophils is necessary for their activation by anti-neutrophil cytoplasm autoantibodies (ANCA) against MPO. Journal of leukocyte biology 48 12773517
2022 MPO/HOCl Facilitates Apoptosis and Ferroptosis in the SOD1G93A Motor Neuron of Amyotrophic Lateral Sclerosis. Oxidative medicine and cellular longevity 45 35178161
2012 Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women. Clinical biochemistry 44 22285381
2008 A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk. Breast cancer research and treatment 43 18340529
2005 Childhood microscopic polyangiitis associated with MPO-ANCA. Pediatric nephrology (Berlin, Germany) 42 16252100
2002 Association between asbestos exposure, cigarette smoking, myeloperoxidase (MPO) genotypes, and lung cancer risk. American journal of industrial medicine 39 12111688
2014 Anti-inflammatory effect of recreational exercise in TNBS-induced colitis in rats: role of NOS/HO/MPO system. Oxidative medicine and cellular longevity 38 24683438
2021 Circulating Myeloperoxidase (MPO)-DNA complexes as marker for Neutrophil Extracellular Traps (NETs) levels and the association with cardiovascular risk factors in the general population. PloS one 37 34379628
2013 Myeloperoxidase (MPO)-specific CD4+ T cells contribute to MPO-anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis. Cellular immunology 35 23665205
2018 Mechanistic Role of the Calcium-Dependent Protease Calpain in the Endothelial Dysfunction Induced by MPO (Myeloperoxidase). Hypertension (Dallas, Tex. : 1979) 33 29507101
2020 Effects of mesalazine combined with bifid triple viable on intestinal flora, immunoglobulin and levels of cal, MMP-9, and MPO in feces of patients with ulcerative colitis. European review for medical and pharmacological sciences 32 32017001
2022 Dual-Positive MPO- and PR3-ANCA-Associated Vasculitis Following SARS-CoV-2 mRNA Booster Vaccination: A Case Report and Systematic Review. Vaccines 31 35632410
2017 Neutrophil activation during acute human anaphylaxis: analysis of MPO and sCD62L. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 31 27906487
2016 Acute phase of aortic dissection: a pilot study on CD40L, MPO, and MMP-1, -2, 9 and TIMP-1 circulating levels in elderly patients. Immunity & ageing : I & A 31 27006681
2008 Natural and disease associated anti-myeloperoxidase (MPO) autoantibodies. Autoimmunity reviews 31 18558355
2004 Involvement of the mpo operon in resistance to class IIa bacteriocins in Listeria monocytogenes. FEMS microbiology letters 29 15336400
2019 Salivary levels of MPO, MMP-8 and TIMP-1 are associated with gingival inflammation response patterns during experimental gingivitis. Cytokine 28 30626536
2019 Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis. Journal of autoimmunity 28 31383567
2018 Evaluation of the oxidative stress-related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population. Diabetes & vascular disease research 28 29383971
2010 Genetic Polymorphisms of CYP2E1, GSTP1, NQO1 and MPO and the Risk of Nasopharyngeal Carcinoma in a Han Chinese Population of Southern China. BMC research notes 28 20663217
2017 Quercetin attenuates the ischemia reperfusion induced COX-2 and MPO expression in the small intestine mucosa. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 28858733
2012 Possible implication of disordered neutrophil extracellular traps in the pathogenesis of MPO-ANCA-associated vasculitis. Clinical and experimental nephrology 26 23224024
2020 Neutrophils as Sentinel Cells of the Immune System: A Role of the MPO-halide-system in Innate and Adaptive Immunity. Current medicinal chemistry 25 31424363
2015 Systemic and coronary levels of CRP, MPO, sCD40L and PlGF in patients with coronary artery disease. BMC research notes 25 26576922
2007 TNF-alpha, TNF-beta, IL-6, IL-10, PECAM-1 and the MPO inflammatory gene polymorphisms in osteosarcoma. Journal of pediatric hematology/oncology 25 17483704
2001 Possible risk reduction in esophageal cancer associated with MPO -463 A allele. Journal of epidemiology 25 11434421
2022 Unexpected Role of MPO-Oxidized LDLs in Atherosclerosis: In between Inflammation and Its Resolution. Antioxidants (Basel, Switzerland) 24 35624738
2017 A putative Chondroprotective role for IL-1β and MPO in herbal treatment of experimental osteoarthritis. BMC complementary and alternative medicine 24 29166937
2022 Clinical Significance of MPO-ANCA in Eosinophilic Granulomatosis With Polyangiitis: Experience From a Longitudinal Chinese Cohort. Frontiers in immunology 23 35833130
2022 NETosis in Psoriatic Arthritis: Serum MPO-DNA Complex Level Correlates With Its Disease Activity. Frontiers in immunology 22 35774788
2016 IL-1β promotes tubulointerstitial injury in 
MPO-ANCA-associated glomerulonephritis
. Clinical nephrology 22 27616759
2021 Comparative Histological Subtyping of Immune Cell Infiltrates in MPO-ANCA and PR3-ANCA Glomerulonephritis. Frontiers in immunology 21 34759920
1996 Cis-elements in the promoter region of the human myeloperoxidase (MPO) gene. Leukemia 21 8683986
2023 In Silico Study in MPO and Molecular Docking of the Synthetic Drynaran Analogues Against the Chronic Tinnitus: Modulation of the M1 Muscarinic Acetylcholine Receptor. Molecular biotechnology 20 37079267
2022 Therapeutic inhibition of MPO stabilizes pre-existing high risk atherosclerotic plaque. Redox biology 20 36375379
2021 DNA Hypomethylation of the MPO Gene in Peripheral Blood Leukocytes Is Associated with Cerebral Stroke in the Acute Phase. Journal of molecular neuroscience : MN 20 33864596
2017 Genetic Variations of Oxidative Stress Related Genes ALOX5, ALOX5AP and MPO Modulate Ischemic Stroke Susceptibility Through Main Effects and Epistatic Interactions in a Chinese Population. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 20 29041000
2021 Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177. Scientific reports 19 34552111
2020 MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease. Journal of cellular physiology 19 32052443
2010 The MPO -463G>A polymorphism and cancer risk: a meta-analysis based on 43 case-control studies. Mutagenesis 19 20418356
2002 Functional activity of three distinct myeloperoxidase (MPO) promoters in human myeloid cells. Leukemia 19 12040446
1994 A myeloid-lineage-specific enhancer upstream of the mouse myeloperoxidase (MPO) gene. Leukemia 19 8182931
1990 Developmental and differential regulation of human MPO gene in leukemic cells. Leukemia 19 2165203
2015 Neutrophil and monocyte responses to downhill running: Intracellular contents of MPO, IL-6, IL-10, pstat3, and SOCS3. Scandinavian journal of medicine & science in sports 18 26059973
1990 Synovial fluid polymorphonuclear leucocytes from patients with rheumatoid arthritis have reduced MPO and NADPH-oxidase activity. British journal of rheumatology 18 2175239
2024 MPO-DNA Complexes and cf-DNA in Patients with Sepsis and Their Clinical Value. Biomedicines 15 39457503
2022 Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA. Rheumatology (Oxford, England) 15 34888651
2022 A homozygous loss-of-function variant in the MPO gene is associated with generalized pustular psoriasis. The Journal of dermatology 15 36585391
2021 New Insights on NETosis Induced by Entamoeba histolytica: Dependence on ROS from Amoebas and Extracellular MPO Activity. Antioxidants (Basel, Switzerland) 15 34206992
2021 Patterns of lung diseases predict survival in patients with MPO-ANCA-associated vasculitis: a single-center retrospective study. Clinical rheumatology 15 34839416
2021 Transcriptomes of MPO-Deficient Patients with Generalized Pustular Psoriasis Reveals Expansion of CD4+ Cytotoxic T Cells and an Involvement of the Complement System. The Journal of investigative dermatology 14 34973310
2009 Overexpression of ZNF342 by juxtaposition with MPO promoter/enhancer in the novel translocation t(17;19)(q23;q13.32) in pediatric acute myeloid leukemia and analysis of ZNF342 expression in leukemia. Genes, chromosomes & cancer 14 19255975
2019 Proteome Analyses Reveal Positive Association of COL2A1, MPO, TYMS, and IGFBP5 with Canine Mammary Gland Malignancy. Proteomics. Clinical applications 13 30578659
2024 FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα-CPT1a pathway. Rheumatology (Oxford, England) 12 38837706
2023 PRTN3 variant correlates with increased autoantigen levels and relapse risk in PR3-ANCA versus MPO-ANCA disease. JCI insight 12 36626226
2021 CircRNA_0079586 and circRNA_RanGAP1 are involved in the pathogenesis of intracranial aneurysms rupture by regulating the expression of MPO. Scientific reports 12 34611229
2020 An unusual presentation of propylthiouracil-induced anti-MPO and PR3 positive ANCA vasculitis with associated anti-GBM antibodies, IgA nephropathy and an IgG4 interstitial infiltrate: a case report. BMC nephrology 12 32703233
2013 The MPO-463G>A polymorphism and lung cancer risk: a meta-analysis based on 22 case-control studies. PloS one 12 23840365
2006 Increased serum levels of S100A12 in patients with MPO-ANCA-associated glomerulonephritis. Clinical nephrology 12 17140160
2021 Hyperactive neutrophils infiltrate vital organs of tumor bearing host and contribute to gradual systemic deterioration via upregulated NE, MPO and MMP-9 activity. Immunology letters 11 34890699
2014 Comparison of a novel chemiluminescence enzyme immunoassay (CLEIA) with enzyme-linked immunosorbent assay (ELISA) for the determination of MPO-ANCA in patients with ANCA-associated vasculitis. Modern rheumatology 11 25388618
1991 Cytochemically unreactive neutrophils from subjects with myeloperoxidase (MPO) deficiency show a complex pattern of immunoreactivity with anti-MPO monoclonal antibodies: a flow cytometric and immunocytochemical study. Annals of hematology 11 1655065
2023 Inhibitor of apoptosis proteins antagonist SM164 ameliorates experimental MPO-ANCA-associated vasculitis via enhancing fatty acid oxidation in neutrophils. Rheumatology (Oxford, England) 10 36308438
2022 Verdiperstat attenuates acute lung injury by modulating MPO/μ-calpain/β-catenin signaling. European journal of pharmacology 10 35461824
2022 The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis. BMC immunology 10 36088289
2020 The diagnostic power of CD117, CD13, CD56, CD64, and MPO in rapid screening acute promyelocytic leukemia. BMC research notes 10 32847610
2018 Expression changes of CD177 and MPO as novel biomarkers in lung tissue of CLP model rats. Turkish journal of medical sciences 10 30543087
2017 Association between MPO-463G > A polymorphism and cancer risk: evidence from 60 case-control studies. World journal of surgical oncology 10 28764808
2016 T47D Cells Expressing Myeloperoxidase Are Able to Process, Traffic and Store the Mature Protein in Lysosomes: Studies in T47D Cells Reveal a Role for Cys319 in MPO Biosynthesis that Precedes Its Known Role in Inter-Molecular Disulfide Bond Formation. PloS one 10 26890638
2015 Therapeutic Potential of Ocimum tenuiflorum as MPO Inhibitor with Implications for Atherosclerosis Prevention. Journal of medicinal food 10 25764050
2014 Immunohistochemical expression of MPO, CD163 and VEGF in inflammatory cells in acute respiratory distress syndrome: a case report. International journal of clinical and experimental pathology 10 25120850
2004 No association of G-463A myeloperoxidase gene polymorphism with MPO-ANCA-associated vasculitis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 10 15031357
2023 Circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of bone marrow mesenchymal stem cells. European journal of pharmacology 9 37981258
2022 Implication of platelets and complement C3 as link between innate immunity and tubulointerstitial injury in renal vasculitis with MPO-ANCA seropositivity. Frontiers in immunology 9 36439156
2017 The association of MPO gene promoter polymorphisms with Alzheimer's disease risk in Chinese Han population. Oncotarget 9 29296208
2015 Association of single nucleotide polymorphisms in MPO and COX genes with oral lichen planus. International journal of immunogenetics 9 25823564
2014 An association between MPO -463 G/A polymorphism and type 2 diabetes. Folia biologica 9 25056433
2021 Polymorphisms in NQO1 and MPO genes and risk for bladder cancer in Tunisian population. Molecular genetics & genomic medicine 8 34549902
2003 Prostanoids and MPO-halide system products as a link between innate and adaptive immunity. Immunology letters 8 14556977