16 results on '"Legssyer R"'
Search Results
2. Azithromycin reduces spontaneous and induced inflammation in F 508 cystic fibrosis mice
- Author
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Legssyer, R, Huaux, F, Lebacq, J, Delos, M, Marbaix, E, Lebecque, P, Lison, D, Scholte, Bob, Legssyer, R, Huaux, F, Lebacq, J, Delos, M, Marbaix, E, Lebecque, P, Lison, D, and Scholte, Bob
- Published
- 2006
3. Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine
- Author
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UCL, Legssyer, R, Josse, C, Piette, J, Ward, Roberta J., Crichton, Robert, UCL, Legssyer, R, Josse, C, Piette, J, Ward, Roberta J., and Crichton, Robert
- Abstract
Both desferrioxamine (DFO) and chloroquine can significantly reduce hepatic iron in experimental animals with iron overload by chelating iron from the low-molecular-weight pool or decreasing iron uptake by the transferrin-transferrin receptor cycle, respectively. However, no previous studies have investigated whether combination therapy of these two drugs would further decrease the tissue iron overload as well as iron-induced toxicity. Chloroquine administration, 15 mg/kg, 5x/week, to rats during the iron loading regime, 10 mg/kg, 3x/week for 4 weeks, significantly decreased both hepatic (54%) and macrophage iron content (24%). However when administered in combination with desferrioxamine, 10 mg/kg, 3x/week for 2 weeks at the cessation of iron loading, no further reduction of hepatic iron content was noted while the iron content of the macrophages significantly increased, possibly indicating the flux of ferrioxamine through these cells. Further studies are warranted to investigate the speciation of iron within these macrophages. Macrophages isolated from chloroquine-treated iron loaded rats showed a reduction in latent NFkappaB activation and a significant increase in lipopolysaccharide-stimulated nitrite release by comparison to these parameters in iron loaded macrophages. Co-administration of chloroquine and desferrioxamine normalised the latent activity of NFkappaB to that of control macrophages as well as increasing LPS-stimulated NO release towards control values. However, DFO alone did not have any significant effect upon either of these parameters. Such results may have important relevance for the reduced immune function of iron loaded macrophages isolated from thalassaemia patients receiving chelation therapy and their propensity to increased infection. (C) 2002 Elsevier Science Inc. All rights reserved.
- Published
- 2003
4. The influence of iron homoeostasis on macrophage function
- Author
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UCL - Autre, Ward, Roberta J., Wilmet, S, Legssyer, R, Crichton, Robert, 3rd International Biometals Symposium (BIOMETALS 2002), UCL - Autre, Ward, Roberta J., Wilmet, S, Legssyer, R, Crichton, Robert, and 3rd International Biometals Symposium (BIOMETALS 2002)
- Abstract
Iron loading of alveolar macrophages in vivo significantly altered their ability to respond to various inflammatory, stimuli. This was exemplified by reduced synthesis of inducible nitric oxide synthase after stimulus with lipopolysaccharide and interferon gamma, and an enhanced activation of nuclear factor kappaB in the absence of tumour necrosis factor alpha stimulation, and enhanced production of reactive oxygen species after activation with activated zymosan and PMA. Such results may indicate an imbalance in the production of reactive oxygen and reactive nitrogen species generated by the iron-loaded macrophages after an appropriate stimulus.
- Published
- 2002
5. Does the haemosiderin iron core determine its potential for chelation and the development of iron-induced tissue damage?
- Author
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UCL - Autre, Ward, Roberta J., Legssyer, R, Henry, C, Crichton, Robert, 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC), UCL - Autre, Ward, Roberta J., Legssyer, R, Henry, C, Crichton, Robert, and 5th International Symposium on Applied Bioinorganic Chemistry (5 ISABC)
- Abstract
Haemosiderin, the major iron storage protein in tissues of iron-loaded tissues shows heterogeneity with respect to both its iron mineralisation product and associated protein. Such mineralisation products have been characterised by a variety of physical techniques including Mossbauer spectroscopy, electron diffraction and EXAFS, and are closely related to the mineral ferrihydrite. A wide range of iron chelators are being developed for the treatment of abnormal haemoglobinopathies, predominantly beta-thalassaemia, which may show greater chelator efficacy for particular mineralisation products of haemosiderin. Even though the tissue iron loadings achieved in different iron-loading syndromes are similar, e.g. naturally occurring iron loading, genetic haemochromatosis and thalassaemia, it is dear that the iron loading in thalassaemic causes extensive damage. The explanation for this could relate to the distribution of iron within different cell types, predominantly reticuloendothelial, its rate of deposition and the mineralisation product of its haemosiderin iron core, goethite. (C) 2000 Elsevier Science Inc. All rights reserved.
- Published
- 2000
6. Effect of chronic chloroquine administration on iron loading in the liver and reticuloendothelial system and on oxidative responses by the alveolar macrophages.
- Author
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UCL - SC/CHIM - Département de chimie, Legssyer, R, Ward, Roberta J., Crichton, Robert, Boelaert, J R, UCL - SC/CHIM - Département de chimie, Legssyer, R, Ward, Roberta J., Crichton, Robert, and Boelaert, J R
- Abstract
The ability of chloroquine to alter iron loading in the liver, spleen, and alveolar macrophages was investigated in iron-loaded or -depleted rats. Chloroquine significantly reduced incorporation of iron into the liver, spleen, and alveolar macrophages of animals loaded in vivo with iron dextran. The ability of these macrophages to respond to oxidative stress was assayed by their capacity to release reactive nitrogen intermediates after lipopolysaccharide (LPS) stimulation. A significant reduction in nitrite release was observed in primary cultures of macrophages isolated from chloroquine/iron dextran-administered rats in comparison to macrophages lavaged from rats iron-loaded alone. Macrophages isolated from iron-deficient rats showed a significant increase in nitrite after LPS stimulation, whereas nitrite release in the macrophages lavaged from the rats which had also received chloroquine during the iron depletion regime was much lower. These results indicate that the use of agents which decrease the iron content and diminish the oxidative response of the cell to altered iron status may be of therapeutic value in patients with iron loading, particularly of the reticuloendothelial system.
- Published
- 1999
7. The influence of iron homoeostasis on macrophage function
- Author
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Ward, R. J., primary, Wilmet, S., additional, Legssyer, R., additional, and Crichton, R. R., additional
- Published
- 2002
- Full Text
- View/download PDF
8. Does the haemosiderin iron core determine its potential for chelation and the development of iron-induced tissue damage?
- Author
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Ward, R. J., Legssyer, R., Henry, C., and Crichton, R. R.
- Published
- 2000
- Full Text
- View/download PDF
9. Effect of chronic chloroquine administration on iron loading in the liver and reticuloendothelial system on oxidative responses by the alveolar macrophages
- Author
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Legssyer, R., Ward, R. J., Crichton, R. R., and Boelaert, J. R.
- Published
- 1999
- Full Text
- View/download PDF
10. Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice
- Author
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Lison Dominique, Lebecque Patrick, Marbaix Etienne, Delos Monique, Lebacq Jean, Huaux François, Legssyer Rachida, Scholte Bob J, Wallemacq Pierre, and Leal Teresinha
- Subjects
Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. Methods We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. Results In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. Conclusion Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation.
- Published
- 2006
- Full Text
- View/download PDF
11. Effects of marginal iron overload on iron homeostasis and immune function in alveolar macrophages isolated from pregnant and normal rats.
- Author
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Ward RJ, Wilmet S, Legssyer R, Leroy D, Toussaint L, Crichton RR, Pierreux C, Hue L, Piette J, Srai SK, Solanky N, Klein D, and Summer K
- Subjects
- Animals, Female, Homeostasis, Immune System, Inflammation, Macrophages metabolism, NADPH Oxidases metabolism, NF-kappa B metabolism, Nitric Oxide Synthase metabolism, Pregnancy, Pregnancy, Animal, Rats, Rats, Wistar, Iron toxicity, Macrophages cytology, Pulmonary Alveoli metabolism
- Abstract
The effects of changes in macrophage iron status, induced by single or multiple iron injections, iron depletion or pregnancy, on both immune function and mRNA expression of genes involved in iron influx and egress have been evaluated. Macrophages isolated from iron deficient rats, or pregnant rats at day 21 of gestation, either supplemented with a single dose of iron dextran, 10 mg, at the commencement of pregnancy, or not, showed significant increases of macrophage ferroportin mRNA expression, which was paralleled by significant decreases in hepatic Hamp mRNA expression. IRP activity in macrophages was not significantly altered by iron status or the inducement of pregnancy +/- a single iron supplement. Macrophage immune function was significantly altered by iron supplementation and pregnancy. Iron supplementation, alone or combined with pregnancy, increased the activities of both NADPH oxidase and nuclear factor kappa B (NFkappaB). In contrast, the imposition of pregnancy reduced the ability of these parameters to respond to an inflammatory stimuli. Increasing iron status, if only marginally, will reduce the ability of macrophages to mount a sustained response to inflammation as well as altering iron homeostatic mechanisms.
- Published
- 2009
- Full Text
- View/download PDF
12. Azithromycin reduces spontaneous and induced inflammation in DeltaF508 cystic fibrosis mice.
- Author
-
Legssyer R, Huaux F, Lebacq J, Delos M, Marbaix E, Lebecque P, Lison D, Scholte BJ, Wallemacq P, and Leal T
- Subjects
- Animals, Chemokine CXCL2, Interleukin-10 biosynthesis, Lipopolysaccharides, Lung drug effects, Lung pathology, Macrophages drug effects, Macrophages pathology, Mice, Mice, Mutant Strains, Monokines metabolism, Neutrophil Infiltration drug effects, Pneumonia chemically induced, Pneumonia metabolism, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents pharmacology, Azithromycin pharmacology, Cystic Fibrosis complications, Cystic Fibrosis genetics, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Pneumonia etiology, Pneumonia pathology
- Abstract
Background: Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice., Methods: We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the DeltaF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated., Results: In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-alpha and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation., Conclusion: Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation.
- Published
- 2006
- Full Text
- View/download PDF
13. Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine.
- Author
-
Legssyer R, Josse C, Piette J, Ward RJ, and Crichton RR
- Subjects
- Animals, Liver metabolism, Macrophages, Alveolar metabolism, Male, Nitric Oxide metabolism, Rats, Rats, Wistar, Spleen metabolism, Chloroquine administration & dosage, Deferoxamine administration & dosage, Iron metabolism, Macrophages, Alveolar physiology
- Abstract
Both desferrioxamine (DFO) and chloroquine can significantly reduce hepatic iron in experimental animals with iron overload by chelating iron from the low-molecular-weight pool or decreasing iron uptake by the transferrin-transferrin receptor cycle, respectively. However, no previous studies have investigated whether combination therapy of these two drugs would further decrease the tissue iron overload as well as iron-induced toxicity. Chloroquine administration, 15 mg/kg, 5x/week, to rats during the iron loading regime, 10 mg/kg, 3x/week for 4 weeks, significantly decreased both hepatic (54%) and macrophage iron content (24%). However when administered in combination with desferrioxamine, 10 mg/kg, 3x/week for 2 weeks at the cessation of iron loading, no further reduction of hepatic iron content was noted while the iron content of the macrophages significantly increased, possibly indicating the flux of ferrioxamine through these cells. Further studies are warranted to investigate the speciation of iron within these macrophages. Macrophages isolated from chloroquine-treated iron loaded rats showed a reduction in latent NFkappaB activation and a significant increase in lipopolysaccharide-stimulated nitrite release by comparison to these parameters in iron loaded macrophages. Co-administration of chloroquine and desferrioxamine normalised the latent activity of NFkappaB to that of control macrophages as well as increasing LPS-stimulated NO release towards control values. However, DFO alone did not have any significant effect upon either of these parameters. Such results may have important relevance for the reduced immune function of iron loaded macrophages isolated from thalassaemia patients receiving chelation therapy and their propensity to increased infection.
- Published
- 2003
- Full Text
- View/download PDF
14. Iron supplementation during pregnancy--a necessary or toxic supplement?
- Author
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Ward RJ, Wilmet S, Legssyer R, and Crichton RR
- Abstract
The effects of a single intramuscular iron dose, 10mg, to pregnant rats on Day of pregnancy, on the outcome of pregnancy, with respect to foetal weight and mother's immune function has been investigated. Despite significantly elevated hepatic iron stores after iron supplementation in pregnant rats this had no significant effect upon blood haemoglobin or transferrin saturation levels. However the mean weight of the foetuses at Day 20-21 was significantly lower than that of the non-supplemented pregnant rats. Iron supplements significantly increased the activity of NADPH oxidase in the maternal alveolar macrophages, the primary event in the formation of the phagolysosome to combat invading organisms. However inducible nitric oxide synthase activity was significantly reduced in these macrophages as shown by decreases in LPSinduced and LPS+IFNgamma-induced NOS activation. Iron supplementation to rats of normal iron status at the commencement of pregnancy did not show any beneficial effects to either the foetus or the mother.
- Published
- 2003
- Full Text
- View/download PDF
15. Molecular and cellular mechanisms of iron homeostasis and toxicity in mammalian cells.
- Author
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Crichton RR, Wilmet S, Legssyer R, and Ward RJ
- Subjects
- Animals, Biological Transport physiology, Brain cytology, Brain metabolism, Chelating Agents metabolism, Heme Oxygenase (Decyclizing) metabolism, Hepatocytes metabolism, Humans, Intestinal Mucosa cytology, Intestinal Mucosa metabolism, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Iron-Regulatory Proteins, Iron-Sulfur Proteins metabolism, Macrophages metabolism, Oxidative Stress, RNA-Binding Proteins metabolism, Reactive Nitrogen Species metabolism, Reactive Oxygen Species metabolism, Transferrin metabolism, Homeostasis, Iron metabolism, Iron toxicity, Iron Overload metabolism
- Abstract
Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing enzymes and proteins, yet it is also toxic. The mechanisms involved in iron absorption across the intestinal tract, its transport in serum and delivery to cells and iron storage within cells is briefly reviewed. Current views on cellular iron homeostasis involving the iron regulatory proteins IRP1 and IRP2 and their interactions with the iron regulatory elements, affecting either mRNA translation (ferritin and erythroid cell delta-aminolaevulinate synthase) or mRNA stability (transferrin receptor) are discussed. The potential of Fe(II) to catalyse hydroxyl radical formation via the Fenton reaction means that iron is potentially toxic. The toxicity of iron in specific tissues and cell types (liver, macrophages and brain) is illustrated by studies with appropriate cellular and animal models. In liver, the high levels of cyoprotective enzymes and antioxidants, means that to observe toxic effects substantial levels of iron loading are required. In reticuloendothelial cells, such as macrophages, relatively small increases in cellular iron (2-3-fold) can affect cellular signalling, as measured by NO production and activation of the nuclear transcription factor NF kappa B, as well as cellular function, as measured by the capacity of the cells to produce reactive oxygen species when stimulated. The situation in brain, where anti-oxidative defences are relatively low, is highly regionally specific, where iron accumulation in specific brain regions is associated with a number of neurodegenerative diseases. In the brains of animals treated with either trimethylhexanoylferrocene or aluminium gluconate, iron and aluminium accumulate, respectively. With the latter compound, iron also increases, which may reflect an effect of aluminium on the IRP2 protein. Chelation therapy can reduce brain aluminium levels significantly, while iron can also be removed, but with greater difficulty. The prospects for chelation therapy in the treatment and possible prevention of neurodegenerative diseases is reviewed.
- Published
- 2002
- Full Text
- View/download PDF
16. Effect of chronic chloroquine administration on iron loading in the liver and reticuloendothelial system and on oxidative responses by the alveolar macrophages.
- Author
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Legssyer R, Ward RJ, Crichton RR, and Boelaert JR
- Subjects
- Animals, Chloroquine administration & dosage, Lipopolysaccharides, Liver metabolism, Macrophages, Alveolar metabolism, Male, Mononuclear Phagocyte System metabolism, Nitrites metabolism, Oxidation-Reduction, Rats, Rats, Wistar, Superoxide Dismutase metabolism, Chloroquine pharmacology, Iron metabolism, Liver drug effects, Macrophages, Alveolar drug effects, Mononuclear Phagocyte System drug effects
- Abstract
The ability of chloroquine to alter iron loading in the liver, spleen, and alveolar macrophages was investigated in iron-loaded or -depleted rats. Chloroquine significantly reduced incorporation of iron into the liver, spleen, and alveolar macrophages of animals loaded in vivo with iron dextran. The ability of these macrophages to respond to oxidative stress was assayed by their capacity to release reactive nitrogen intermediates after lipopolysaccharide (LPS) stimulation. A significant reduction in nitrite release was observed in primary cultures of macrophages isolated from chloroquine/iron dextran-administered rats in comparison to macrophages lavaged from rats iron-loaded alone. Macrophages isolated from iron-deficient rats showed a significant increase in nitrite after LPS stimulation, whereas nitrite release in the macrophages lavaged from the rats which had also received chloroquine during the iron depletion regime was much lower. These results indicate that the use of agents which decrease the iron content and diminish the oxidative response of the cell to altered iron status may be of therapeutic value in patients with iron loading, particularly of the reticuloendothelial system.
- Published
- 1999
- Full Text
- View/download PDF
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