Polymorphonuclear neutrophils (PMNs) play a key role in host defense. However, their massive accumulation at the site of inflammation can delay regenerative healing processes and can initiate pathological inflammatory processes. Thus, the efficient clearance of PMNs mediated by the induction of regulated cell death is a key process preventing the development of these pathological conditions. Myeloperoxidase (MPO), a highly abundant enzyme in PMN granules, primarily connected with PMN defense machinery, is suggested to play a role in PMN-regulated cell death. However, the contribution of MPO to the mechanisms of PMN cell death remains incompletely characterized. Herein, the process of the cell death of mouse PMNs induced by three different stimuli - phorbol 12-myristate 13-acetate (PMA), opsonized streptococcus (OST), and N-formyl-met-leu-phe (fMLP) - was investigated. MPO-deficient PMNs revealed a significantly decreased rate of cell death characterized by phosphatidylserine surface exposure and cell membrane permeabilization. An inhibitor of MPO activity, 4-aminobenzoic acid hydrazide, did not exhibit a significant effect on PMA-induced cell death compared to MPO deficiency. Interestingly, only the limited activation of markers related to apoptotic cell death was observed (e.g. caspase 8 activation, Bax expression) and they mostly did not correspond to phosphatidylserine surface exposure. Furthermore, a marker characterizing autophagy, cleavage of LC3 protein, as well as histone H3 citrullination and its surface expression was observed. Collectively, the data show the ability of MPO to modulate the life span of PMNs primarily through the potentiation of cell membrane permeabilization and phosphatidylserine surface exposure.

• MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Neutrophils metabolism   pathology   MeSH
• Peroxidase deficiency   metabolism   MeSH
• Regulated Cell Death MeSH
• Inflammation metabolism   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. METHODS: Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. RESULTS: From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76-100%) versus those enrolling patients with and without kidney involvement (56%, 45-66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. CONCLUSIONS: In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice.

• MeSH
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * drug therapy   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Remission Induction MeSH
• Mycophenolic Acid therapeutic use   MeSH
• Humans MeSH
• Microscopic Polyangiitis * MeSH
• Peroxidase MeSH
• Antibodies, Antineutrophil Cytoplasmic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Systematic Review MeSH

Kontext: Myeloperoxidáza se účastní proaterogenních biologických aktivit souvisejících s rozvojem kardiovaskulárních onemocnění včetně vzniku, postupu a akutních komplikací procesu aterosklerózy. Cíl studie: Naším cílem bylo zjistit vztah mezi hodnotami myeloperoxidázy (MPO) v ústí koronárních tepen a závažností ischemické choroby srdeční (ICHS). Metody: Populace našich pacientů byly rozdělena do dvou skupin, A a B. Do skupiny A bylo zařazeno 43 pacientů s infarktem myokardu bez elevací úseku ST (non-ST elevation myocardial infarction, NSTEMI), u nichž bylo provedeno koronarografické vyšetření. Skupina B zahrnovala 43 pacientů bez ICHS prokázané zátěžovým EKG nebo zátěžovým vyšetřením perfuze s thalliem. Hodnoty MPO se stanovovaly ze vzorků krve odebrané z ústí koronárních tepen v skupině s ICHS a vzorků periferní krve u obou skupin. Závažnost ICHS se hodnotila pomocí skórovacích systémů Gensini a CASS. Výsledky: Mezi oběma skupinami byl nalezen významný rozdíl v hodnotách MPO (p = 0,002). Při použití obou skórovacích systémů hodnoty MPO v séru korelovaly se závažností ICHS (Gensini; p = 0,002 a CASS; p = 0,05). Ve skupině s ICHS korelovaly hodnoty MPO ve vzorcích periferní krve i ve vzorcích odebraných z ústí koronárních tepen. Závěry: Hodnoty MPO v séru korelovaly se závažností ischemické choroby srdeční. Hodnoty MPO v periferní krvi odrážely hodnoty MPO naměřené v krvi odebrané z ústí koronárních tepen. Koronární ostium je jednoduché, přístupné a spolehlivé místo pro odběr vzorků krve z koronárních tepen.

Background: Myeloperoxidase participates in proatherogenic biological activities related to the evolution of cardiovascular disease including initiation, propagation, and acute complications of atherosclerotic process. Aim of study: We aimed to identify the relationship between myeloperoxidase (MPO) level at the ostium of coronary arteries and severity of coronary artery disease (CAD) . Methods: Our study population was divided into two groups: group A and B. Group A included 43 patients with non-ST elevation myocardial infarction (NSTEMI) who underwent coronary angiography. Group B included 43 subjects free from CAD as proved by stress ECG or stress thallium study. MPO level was assessed by coronary osteal sampling of CAD group and peripheral venous sampling of both groups. The severity of CAD was studied using the Gensini & CASS scores. Results: There was a significant difference in MPO level between both groups (p = 0.002) . Serum MPO was correlated to coronary artery disease as evaluated using Gensini score (p = 0.002) & CASS score (p = 0.05). Peripheral venous sample of MPO correlated with coronary osteal samples in CAD group. Conclusions: Serum MPO was correlated to severity of coronary artery disease. The peripheral venous level of MPO reflected the osteal coronary levels of MPO. Coronary ostium is a simple, accessible and reliable site for coronary sampling.

• MeSH
• Acute Coronary Syndrome diagnosis   pathology   MeSH
• Myocardial Ischemia * diagnosis   blood   MeSH
• Clinical Studies as Topic MeSH
• Coronary Vessels MeSH
• Humans MeSH
• Blood Specimen Collection MeSH
• Peroxidase * MeSH
• Severity of Illness Index MeSH
• Check Tag
• Humans MeSH

Endothelial cell (EC) glycocalyx (GLX) comprise a multicomponent layer of proteoglycans and glycoproteins. Alteration of its integrity contributes to chronic vascular inflammation and leads to the development of cardiovascular diseases. Myeloperoxidase (MPO), a highly abundant enzyme released by polymorphonuclear neutrophils, binds to the GLX and deleteriously affects vascular EC functions. The focus of this study was to elucidate the mechanisms of MPO-mediated alteration of GLX molecules, and to unravel subsequent changes in endothelial integrity and function. MPO binding to GLX of human ECs and subsequent internalization was mediated by cell surface heparan sulfate chains. Moreover, interaction of MPO, which is carrying a cationic charge, with anionic glycosaminoglycans (GAGs) resulted in reduction of their relative charge. By means of micro-viscometry and atomic force microscopy, we disclosed that MPO can crosslink GAG chains. MPO-dependent modulation of GLX structure was further supported by alteration of wheat germ agglutinin staining. Increased expression of ICAM-1 documented endothelial cell activation by both catalytically active and also inactive MPO. Furthermore, MPO increased vascular permeability connected with reorganization of intracellular junctions, however, this was dependent on MPO's catalytic activity. Novel proteins interacting with MPO during transcytosis were identified by proteomic analysis. Altogether, these findings provide evidence that MPO through interaction with GAGs modulates overall charge of the GLX, causing modification of its structure and thus affecting EC function. Importantly, our results also suggest a number of proteins interacting with MPO that possess a variety of cellular localizations and functions.

• MeSH
• Endothelium, Vascular MeSH
• Endothelial Cells MeSH
• Humans MeSH
• Neutrophils MeSH
• Peroxidase * MeSH
• Proteomics * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

N-acetylcysteine (NAC), often used as an antioxidant-scavenging reactive oxygen species (ROS) in vitro, was recently shown to increase the cytotoxicity of other compounds through ROS-dependent and ROS-independent mechanisms. In this study, NAC itself was found to induce extensive ROS production in human leukemia HL-60 and U937 cells. The cytotoxicity depends on ROS-modulating enzyme expression. In HL-60 cells, NAC activated NOX2 to produce superoxide (O2•-). Its subsequent conversion into H2O2 by superoxide dismutase 1 and 3 (SOD1, SOD3) and production of ClO- from H2O2 by myeloperoxidase (MPO) was necessary for cell death induction. While the addition of extracellular SOD potentiated NAC-induced cell death, extracellular catalase (CAT) prevented cell death in HL-60 cells. The MPO inhibitor partially reduced the number of dying HL-60 cells. In U937 cells, the weak cytotoxicity of NAC is probably caused by lower expression of NOX2, SOD1, SOD3, and by the absence of MOP expression. However, even here, the addition of extracellular SOD induced cell death in U937 cells, and this effect could be reversed by extracellular CAT. NAC-induced cell death exhibited predominantly apoptotic features in both cell lines. Conclusions: NAC itself can induce extensive production of O2•- in HL-60 and U937 cell lines. The fate of the cells then depends on the expression of enzymes that control the formation and conversion of ROS: NOX, SOD, and MPO. The mode of cell death in response to NAC treatment bears apoptotic and apoptotic-like features in both cell lines.

• MeSH
• Acetylcysteine pharmacology   MeSH
• HL-60 Cells MeSH
• Catalase genetics   MeSH
• Leukemia drug therapy   genetics   metabolism   MeSH
• Humans MeSH
• NADPH Oxidase 2 genetics   MeSH
• Oxidative Stress drug effects   MeSH
• Peroxidase genetics   MeSH
• Cell Proliferation drug effects   MeSH
• Reactive Oxygen Species metabolism   MeSH
• Gene Expression Regulation, Neoplastic drug effects   MeSH
• Gene Expression Profiling MeSH
• Superoxide Dismutase genetics   MeSH
• U937 Cells MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Given its myeloid-restricted expression, myeloperoxidase (MPO) is typically used for lineage assignment (myeloid vs. lymphoid) during acute leukaemia (AL) diagnostics. In the present study, a robust flow cytometric definition for MPO positivity was established based on the standardised EuroFlow protocols, the standardised Acute Leukaemia Orientation Tube and 1734 multicentre AL cases (with confirmed assay stability). The best diagnostic performance was achieved by defining MPO positivity as ≥20% of the AL cells exceeding a lymphocyte-based threshold. The methodology employed should be applicable to any form of standardised flow cytometry.

• MeSH
• Acute Disease MeSH
• Immunophenotyping standards   MeSH
• Leukemia * diagnosis   enzymology   immunology   MeSH
• Humans MeSH
• Neoplasm Proteins * blood   immunology   MeSH
• Peroxidase * blood   immunology   MeSH
• Flow Cytometry standards   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, the United Kingdom, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide (CYC), rituximab (RTX), and corticosteroids the first 3 months was registered. Outcomes up to 2 years from diagnosis included Vasculitis Damage Index (VDI), hospitalization, and cause of death. RESULTS: Treatment data were available for 167 of 202 patients. At 2 years, 4% had no items of damage. There was a positive association between VDI score at 2 years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using CYC or RTX. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. Myeloperoxidase-antineutrophil cytoplasmic antibody positivity and lower creatinine levels decreased the odds of readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with CYC or RTX in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first 3 months was associated with treatment-related damage and fatal infections.

• MeSH
• Granulomatosis with Polyangiitis * complications   drug therapy   MeSH
• Hospitalization MeSH
• Humans MeSH
• Microscopic Polyangiitis * drug therapy   MeSH
• Peroxidase MeSH
• Antibodies, Antineutrophil Cytoplasmic MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Aged MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Azathioprine therapeutic use   MeSH
• Cyclophosphamide therapeutic use   MeSH
• Granulomatosis with Polyangiitis complications   drug therapy   MeSH
• Immunosuppressive Agents therapeutic use   MeSH
• Humans MeSH
• Microscopic Polyangiitis complications   drug therapy   MeSH
• Myeloblastin immunology   MeSH
• Kidney Diseases etiology   physiopathology   MeSH
• Peroxidase immunology   MeSH
• Antibodies, Antineutrophil Cytoplasmic * MeSH
• Recurrence MeSH
• Rituximab therapeutic use   MeSH
• Maintenance Chemotherapy MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Cíl studie: Shrnutí aktuálních poznatků o jednotlivých subpopulacích neutrofilů a jejich roli u preeklampsie. Typ studie: Přehledový článek. Název a sídlo pracoviště: Ústav imunologie a mikrobiologie, 1. lékařská fakulta Univerzity Karlovy a Všeobecné fakultní nemocnice Praha. Úvod: Preeklampsie představuje v současné době jednu z nejzávažnějších těhotenských komplikací s vysokou úmrtností. Preeklampsie je multifaktoriálním onemocněním a dosud nebyla identifikována jasná příčina jejího rozvoje. V průběhu preeklampsie dochází v prostředí placenty k patofyziologickému zvýšení zánětlivé odpovědi. Indukce zánětu vede k migraci velkého počtu neutrofilů, které, jak se v poslední době ukazuje, jsou značně heterogenní populací. Deregulace poměru imunoregulačních subpopulací, jejichž součástí jsou polymorfonukleární myeloidní supresorové buňky, a prozánětlivých subpopulací neutrofilů může přispívat k podpoře zánětlivého prostředí na feto–maternálním rozhraní a rozvoji těhotenských komplikací, mezi něž patří například preeklampsie. Metodika a výsledky: V tomto přehledovém článku je stručně uvedena problematika preeklampsií a výčet různých subpopulací neutrofilů uvedených v literatuře. Závěr: Lepší pochopení role abnormálních subpopulací neutrofilů migrujících do zánětlivého prostředí placent žen s preeklampsií a jejich role v rozvoji této těhotenské komplikace by mohla pomoci odhalit možné terapeutické cíle.

Objective: Review of current knowledge about particular neutrophil subsets and their role in preeclampsia. Design: Review. Setting: Institute of Immunology and Microbiology, First Faculty of Medicine Charles University and General University Hospital in Prague. Introduction: Preeclampsia represents one of the major complications of pregnancy with high mortality nowadays. Preeclampsia is a multifactorial disease and to this date, there has not been clear disease trigger identified. Throughout preeclampsia development, an increase in pathophysiological inflammatory response is being present. The induction of inflammation leads to higher number of migrating neutrophils. Current studies demonstrate that neutrophils are a rather heterogeneous population. Deregulation of the ratio between immunoregulatory subpopulations, including polymorphonuclear myeloid-derived suppressor cells, and proinflammatory neutrophil subpopulations could contribute to the induction of inflammatory environment at the feto–maternal interface and subsequently could promote development of pregnancy complications, such as preeclampsia. Methods and results: In this review, topic of preeclampsia is briefly introduced and a list of distinct neutrophil subsets published in literature is presented. Conclusion: Unravelling the role of abnormal neutrophil subpopulations migrating to the inflammatory environment of preeclamptic placentas and their role in preeclampsia development could help to identify possible therapeutic targets.

• Keywords
• polymorfonukleární myeloidní supresorové buňky,
• MeSH
• Pregnancy Complications MeSH
• Humans MeSH
• Neutrophils MeSH
• Peroxidase MeSH
• Pre-Eclampsia * physiopathology   MeSH
• Pregnancy MeSH
• Inflammation MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Industrial synthetic dyes cause health and environmental problems. This work describes the isolation of 84 bacterial strains from the midgut of the Lasius niger ant and the evaluation of their potential application in dye bioremediation. Strains were identified and classified as judged by rRNA 16S. The most abundant isolates were found to belong to Actinobacteria (49%) and Firmicutes (47.2%). We analyzed the content in laccase, azoreductase and peroxidase activities and their ability to degrade three known dyes (azo, thiazine and anthraquinone) with different chemical structures. Strain Ln26 (identified as Brevibacterium permense) strongly decolorized the three dyes tested at different conditions. Strain Ln78 (Streptomyces ambofaciens) exhibited a high level of activity in the presence of Toluidine Blue (TB). It was determined that 8.5 was the optimal pH for these two strains, the optimal temperature conditions ranged between 22 and 37 °C, and acidic pHs and temperatures around 50 °C caused enzyme inactivation. Finally, the genome of the most promising candidate (Ln26, approximately 4.2 Mb in size) was sequenced. Genes coding for two DyP-type peroxidases, one laccase and one azoreductase were identified and account for the ability of this strain to effectively oxidize a variety of dyes with different chemical structures.

• MeSH
• Actinobacteria enzymology   isolation & purification   metabolism   MeSH
• Bacteria enzymology   isolation & purification   metabolism   MeSH
• Coloring Agents isolation & purification   metabolism   MeSH
• Biodegradation, Environmental MeSH
• Biotechnology MeSH
• Brevibacterium enzymology   isolation & purification   metabolism   MeSH
• Firmicutes enzymology   isolation & purification   metabolism   MeSH
• Ants microbiology   MeSH
• Laccase isolation & purification   metabolism   MeSH
• Environmental Pollutants isolation & purification   metabolism   MeSH
• NADH, NADPH Oxidoreductases isolation & purification   metabolism   MeSH
• Peroxidase isolation & purification   metabolism   MeSH
• Streptomyces enzymology   isolation & purification   metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH