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Jay W Heinecke – One of the best experts on this subject based on the ideXlab platform.

Anthony J Kettle – One of the best experts on this subject based on the ideXlab platform.

  • Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis
    , 2013
    Co-Authors: Anthony J Kettle, Anna L.p. Chapman, Revathy Senthilmohan, Timothy Chan, Iris Osberg, Tessa J. Mocatta, Jeffrey S. Wagener
    Abstract:

    Cystic fibrfibrosis (CF) is characterized by considerable oxidative stress. However, it is not known whether oxidative stress is an important feature early in this disease. We have investigated a group of infants and young children with CF to establish whether oxidants are produced in their airways. Bronchoalveolar lavalavageid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic inflammation, and 3Chlorotyrosine as a biomarker of the potent oxidant hypochlorous acid, which is formed by myeloperoxidase. Protein carbonyls were also measured as a nonspecific indicator of reactive oxidant production. Myeloperoxidase and 3Chlorotyrosine levels in BALF from children with CF were 10- and fivefold higher, respectively, than in disease control subjects. There was a strong correlation between myeloperoxidase and 3Chlorotyrosine. Myeloperoxidase levels were fourfold higher in children with infections in their airways. Median protein carbonyls were elevated by only twofold compared with disease control subjects, but some children had extremely high levels of protein oxidation. We conclude that hypochlorous acid is produced early in CF and that it is a candidate for precipitating the fatal decline in lung function associated with this disease. Also, there must be other sources of oxidants because protein carbonyls were not related to either inflammation or infection

  • Measuring chlorine bleach in biology and medicine.
    Biochimica et biophysica acta, 2013
    Co-Authors: Anthony J Kettle, Anna L.p. Chapman, Irada Khalilova, Amelia M. Albrett, Nina Dickerhof, Louisa V. Forbes, Rufus Turner
    Abstract:

    Abstract Background Chlorine bleach, or hypochlorous acid, is the most reactive two-electron oxidant produced in appreciable amounts in our bodies. Neutrophils are the main source of hypochlorous acid. These champions of the innate immuimmune system use it to fight infection but also direct it against host tissue in inflammatory diseases. Neutrophils contain a rich supply of the enzyme myeloperoxidase. It uses hydrogen peroxide to convert chloride to hypochlorous acid. Scope of review We give a critical appraisal of the best methods to measure production of hypochlorous acid by purified peroxidases and isolated neutrophils. Robust ways of detecting it inside neutrophil phagosomes where bacteria are killed are also discussed. Special attention is focused on reaction-based fluorescent probes but their visual charm is tempered by stressing their current limitations. Finally, the strengths and weaknesses of biomarker assays that capture the footprints of chlorine in various pathologies are evaluated. Major conclusions Detection of hypochlorous acid by purified peroxidases and isolated neutrophils is best achieved by measuring accumulation of taurine chloramine. Formation of hypochlorous acid inside neutrophil phagosomes can be tracked using mass spectrometric analysis of 3Chlorotyrosine and methionine sulfoxide in bacterial protproteins, or detection of chlorinated fluorescein on ingestible particles. Reaction-based fluorescent probes can also be used to monitor hypochlorous acid during phagocytosis. Specific biomarkers of its formation during inflammation include 3Chlorotyrosine, chlorinated products of plasmalogens, and glutathione sulfonamide. General significance These methods should bring new insights into how chlorine bleach is produced by peroxidases, reacts within phagosomes to kill bacteria, and contributes to inflammation. This article is part of a Special Issue entitled Current methods to study reactive oxygen species – pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn.

  • myeloperoxidase and oxidative stress in rheumatoid arthritis
    Rheumatology, 2012
    Co-Authors: Lisa K Stamp, Revathy Senthilmohan, Irada Khalilova, Joanna M Tarr, Rufus Turner, Richard Haigh, Paul G Winyard, Anthony J Kettle
    Abstract:

    Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. Results. Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.214.2; P 3.2) and those with low disease activity (LDA; DAS-28 43.2) (HDA 27.9 ng/ml, 20.234.1 vs LDA 22.1 ng/ml, 16.934.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.42433.0 vs 30.2 ng/ml, IQR 25.150.9; P < 0.0001). The MPO present in SF was mostly active. 3Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3Chlorotyrosine (r = 0.66; P = 0.003).

Revathy Senthilmohan – One of the best experts on this subject based on the ideXlab platform.

  • Myeloperoxidase and Protein Oxidation in the Airways of Young Children with Cystic Fibrosis
    , 2013
    Co-Authors: Anthony J Kettle, Anna L.p. Chapman, Revathy Senthilmohan, Timothy Chan, Iris Osberg, Tessa J. Mocatta, Jeffrey S. Wagener
    Abstract:

    Cystic fibrosis (CF) is characterized by considerable oxidative stress. However, it is not known whether oxidative stress is an important feature early in this disease. We have investigated a group of infants and young children with CF to establish whether oxidants are produced in their airways. Bronchoalveolar lavage fluid (BALF) was assayed for myeloperoxidase as a measure of neutrophilic inflammation, and 3Chlorotyrosine as a biomarker of the potent oxidant hypochlorous acid, which is formed by myeloperoxidase. Protein carbonyls were also measured as a nonspecific indicator of reactive oxidant production. Myeloperoxidase and 3Chlorotyrosine levels in BALF from children with CF were 10- and fivefold higher, respectively, than in disease control subjects. There was a strong correlation between myeloperoxidase and 3Chlorotyrosine. Myeloperoxidase levels were fourfold higher in children with infections in their airways. Median protein carbonyls were elevated by only twofold compared with disease control subjects, but some children had extremely high levels of protein oxidation. We conclude that hypochlorous acid is produced early in CF and that it is a candidate for precipitating the fatal decline in lung function associated with this disease. Also, there must be other sources of oxidants because protein carbonyls were not related to either inflammation or infection

  • myeloperoxidase and oxidative stress in rheumatoid arthritis
    Rheumatology, 2012
    Co-Authors: Lisa K Stamp, Revathy Senthilmohan, Irada Khalilova, Joanna M Tarr, Rufus Turner, Richard Haigh, Paul G Winyard, Anthony J Kettle
    Abstract:

    Objective. To determine whether MPO contributes to oxidative stress and disease activity in RA and whether it produces hypochlorous acid in SF. Methods. Plasma and where possible SF were collected from 77 RA patients while 120 healthy controls supplied plasma only. MPO and protein carbonyls were measured by ELISAs. 3Chlorotyrosine in proteins and allantoin in plasma were measured by mass spectrometry. Results. Plasma MPO concentrations were significantly higher in patients with RA compared with healthy controls [10.8 ng/ml, inter-quartile range (IQR): 7.214.2; P 3.2) and those with low disease activity (LDA; DAS-28 43.2) (HDA 27.9 ng/ml, 20.234.1 vs LDA 22.1 ng/ml, 16.934.9; P > 0.05). There was a significant relationship between plasma MPO and DAS-28 (r = 0.35; P = 0.005). Plasma protein carbonyls and allantoin were significantly higher in patients with RA compared with the healthy controls. MPO protein was significantly higher in SF compared with plasma (median 624.0 ng/ml, IQR 258.42433.0 vs 30.2 ng/ml, IQR 25.150.9; P < 0.0001). The MPO present in SF was mostly active. 3Chlorotyrosine, a specific biomarker of hypochlorous acid, was present in proteins from SF and related to the concentration of MPO (r = 0.69; P = 0.001). Protein carbonyls in SF were associated with MPO protein concentration (r = 0.40; P = 0.019) and 3Chlorotyrosine (r = 0.66; P = 0.003).

  • plasma concentrations of myeloperoxidase predict mortality after myocardial infarction
    Journal of the American College of Cardiology, 2007
    Co-Authors: Tessa J. Mocatta, Revathy Senthilmohan, Anna P Pilbrow, Vicky A Cameron, Chris Frampton, Mark A Richards, Christine C Winterbourn
    Abstract:

    Objectives This study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infainfarction (MI). Background Reactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes. Methods Detailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission. Plasma levels of MPO and protein carbonyls were measured in patients and 156 heart-healthy control subjects. 3Chlorotyrosine was measured in selected patients. Patient mortality was followed for 5 years. Results Plasma MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p Conclusions Myeloperoxidase and protein carbonyl levels are elevated in plasma after acute MI, apparently via independent mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic value to LVEF and plasma NT-proBNP measurements.

Christine C Winterbourn – One of the best experts on this subject based on the ideXlab platform.

  • plasma concentrations of myeloperoxidase predict mortality after myocardial infarction
    Journal of the American College of Cardiology, 2007
    Co-Authors: Tessa J. Mocatta, Revathy Senthilmohan, Anna P Pilbrow, Vicky A Cameron, Chris Frampton, Mark A Richards, Christine C Winterbourn
    Abstract:

    Objectives This study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI). Background Reactive oxidants are implicated in cardiovascular disease, and elevated plasma MPO is reported to predict adverse outcome in acute coronary syndromes. Methods Detailed demographic information, radionuclide ventriculography, neurohormone measurements, and clinical history were obtained for 512 acute MI patients at hospital admission. Plasma levels of MPO and protein carbonyls were measured in patients and 156 heart-healthy control subjects. 3Chlorotyrosine was measured in selected patients. Patient mortality was followed for 5 years. Results Plasma MPO and protein carbonyl concentrations were higher in MI patients 24 h to 96 h after admission than in control subjects (medians: MPO 55 ng/ml vs. 39 ng/ml, and protein carbonyls 48 pmol/mg vs. 17 pmol/mg protein, p Conclusions Myeloperoxidase and protein carbonyl levels are elevated in plasma after acute MI, apparently via independent mechanisms. High MPO is a risk factor for long-term mortality and adds prognostic value to LVEF and plasma NT-proBNP measurements.

  • 3 Chlorotyrosine as a marker of protein damage by myeloperoxidase in tracheal aspirates from preterm infants association with adverse respiratory outcome
    Pediatric Research, 2003
    Co-Authors: Hendrikje I Buss, Anthony J Kettle, Revathy Senthilmohan, Brian A Darlow, N Mogridge, Christine C Winterbourn
    Abstract:

    Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3Chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight <1500 g. 3Chlorotyrosine levels were higher in these infants than in larger infants without respiratory distress (median 83 compared with 13 μmol/mol tyrosine). They correlated strongly with myeloperoxidase activity (correlation coefficient 0.75, p < 0.0001) and to a lesser extent with protein carbonyls. 3Chlorotyrosine levels (at 1 wk after birth) correlated negatively with birth weight or gestational age. They were significantly higher in infants who developed chronic lung disease (oxygen requirement at 36 wk postmenstrual age) than in those who did not (median 88 and 49 μmol/mol tyrosine, respectively) and correlated with days of supplemental oxygen. 3Chlorotyrosine was also significantly higher in infants who had lung infection or were Ureaplasma urealyticum positive. Our results are the first evidence that chlorinated proteins are produced in the lungs of premature infants and that they are higher in infection. The higher 3Chlorotyrosine levels in infants who develop chronic lung disease suggest that neutrophil oxidants contribute to the pathology of this disease.

  • 3Chlorotyrosine as a Marker of Protein Damage by Myeloperoxidase in Tracheal Aspirates From Preterm Infants: Association With Adverse Respiratory Outcome
    Pediatric Research, 2003
    Co-Authors: I Hendrikje Buss, Anthony J Kettle, Revathy Senthilmohan, Brian A Darlow, N Mogridge, Christine C Winterbourn
    Abstract:

    Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3Chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight

Steven G. Boxer – One of the best experts on this subject based on the ideXlab platform.