The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Niels Høiby - One of the best experts on this subject based on the ideXlab platform.
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Pseudomonas aeruginosa alginate in cystic fibrosis sputum and the inflammatory response
Infection and Immunity, 1990Co-Authors: S. S. Pedersen, Arsalan Kharazmi, Frank Espersen, Niels HøibyAbstract:Alginate, a viscous polysaccharide from mucoid Pseudomonas aeruginosa, may interfere with the host defenses in patients with cystic fibrosis and chronic P. aeruginosa lung infection. The alginate concentration in the sol phase of expectorated sputum was quantitated by a biochemical method and a newly developed enzyme-linked immunosorbent assay. There was a high degree of correlation between the methods, and the concentration of alginate ranged from 4 to 101 micrograms/ml with a median of 35.5 micrograms/ml when measured by enzyme-linked immunosorbent assay. Alginate could not be detected in the bronchial secretions from patients without P. aeruginosa infection. In vitro investigation of alginate did not show any activation of the alternative pathway of complement, as determined by a hemolytic kinetic assay and by testing for neutrophil chemotaxis. At a high concentration, P. aeruginosa alginate caused a slight activation of the classical pathway of complement. Alginate did not cause neutrophil chemotaxis by itself but was able to reduce the neutrophil chemotactic response to N-Formylmethionylleucylphenylalanine and for zymosan-activated serum. P. aeruginosa and seaweed alginates were able to prime neutrophils for increased N-Formylmethionylleucylphenylalanine-induced neutrophil oxidative burst, as determined by chemiluminescence. Because of its ability to prevent attraction of neutrophils to the site of infection, lack of complement activation, and ability to enhance neutrophil oxidative burst, alginate from P. aeruginosa may contribute to the persistence and pathogenesis of chronic P. aeruginosa infection in cystic fibrosis.
Andrew W Murray - One of the best experts on this subject based on the ideXlab platform.
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the neutrophil respiratory burst responses to fatty acids n Formylmethionylleucylphenylalanine and phorbol ester suggest divergent signalling mechanisms
FEBS Journal, 1991Co-Authors: Stephen J Hardy, Brenton S Robinson, A Poulos, Dianne P Harvey, Antonio Ferrante, Andrew W MurrayAbstract:The oxygen-dependent respiratory burst is a key neutrophil function required for the killing of bacteria. However, despite intensive investigation, the molecular events which initiate the respiratory burst remain unclear. Recent reports have suggested the agonist-induced hydrolysis of cellular phosphatidylcholine (PtdCho) by phospholipase D may be an essential requirement for initiating or mediating the respiratory burst. We have investigated the effects of the chemotactic peptide N-Formylmethionylleucylphenylalanine (fMLF), the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and the polyunsaturated fatty acids arachidonic [20:4 (n-6)] and docosahexaenoic [22:6 (n-3)] acids in light of this hypothesis. Ethanol-inhibited superoxide production in response to 20:4, 22:6 and fMLF, in a dose-dependent fashion, suggesting an involvement of phospholipase D. The phosphatidic-acid phosphohydrolase inhibitor DL-propranolol completely inhibited superoxide production induced by both 20:4 and 22:6, and partially inhibited the response to TPA. In contrast, superoxide production in response to fMLF was increased by propranolol. fMLF and TPA, but not the fatty acids, stimulated phospholipase D as indicated by the accumulation of phosphatidic acid and, in the presence of ethanol, phosphatidylethanol derived from PtdCho. Extracellular Ca2+ was found to be an essential requirement for fMLF-induced superoxide production. However, responses to the fatty acids were dramatically enhanced under Ca2+.-free conditions. Responses to TPA were independent of the extracellular Ca2+ concentration. Both fatty acids and fMLF, but not TPA, mobilised Ca2+ from intracellular stores, a response insensitive to the effects of both ethanol and propranolol. These results show that, unlike fMLF and TPA, the fatty acids do not cause hydrolysis of PtdCho by phospholipase D. However, the data indirectly suggests that the fatty acids may initiate the phospholipase-d-catalysed hydrolysis of phospholipids other than PtdCho.
S. S. Pedersen - One of the best experts on this subject based on the ideXlab platform.
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Pseudomonas aeruginosa alginate in cystic fibrosis sputum and the inflammatory response
Infection and Immunity, 1990Co-Authors: S. S. Pedersen, Arsalan Kharazmi, Frank Espersen, Niels HøibyAbstract:Alginate, a viscous polysaccharide from mucoid Pseudomonas aeruginosa, may interfere with the host defenses in patients with cystic fibrosis and chronic P. aeruginosa lung infection. The alginate concentration in the sol phase of expectorated sputum was quantitated by a biochemical method and a newly developed enzyme-linked immunosorbent assay. There was a high degree of correlation between the methods, and the concentration of alginate ranged from 4 to 101 micrograms/ml with a median of 35.5 micrograms/ml when measured by enzyme-linked immunosorbent assay. Alginate could not be detected in the bronchial secretions from patients without P. aeruginosa infection. In vitro investigation of alginate did not show any activation of the alternative pathway of complement, as determined by a hemolytic kinetic assay and by testing for neutrophil chemotaxis. At a high concentration, P. aeruginosa alginate caused a slight activation of the classical pathway of complement. Alginate did not cause neutrophil chemotaxis by itself but was able to reduce the neutrophil chemotactic response to N-Formylmethionylleucylphenylalanine and for zymosan-activated serum. P. aeruginosa and seaweed alginates were able to prime neutrophils for increased N-Formylmethionylleucylphenylalanine-induced neutrophil oxidative burst, as determined by chemiluminescence. Because of its ability to prevent attraction of neutrophils to the site of infection, lack of complement activation, and ability to enhance neutrophil oxidative burst, alginate from P. aeruginosa may contribute to the persistence and pathogenesis of chronic P. aeruginosa infection in cystic fibrosis.
Hitoshi Arita - One of the best experts on this subject based on the ideXlab platform.
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synergistic effect of throm ane a2 and n Formylmethionylleucylphenylalanine on platelet activating factor synthesis in human polymorphonuclear neutrophils
Biochimica et Biophysica Acta, 1991Co-Authors: Junji Kishino, Kohji Hanasaki, Toshiyuki Kato, Hitoshi AritaAbstract:Abstract The effects of throm☐ane A 2 (TXA 2 ) on the synthesis of platelet-activating factor (PAF) and leukotriene B 4 (LTB 4 ) were studied using human polymorphonuclear neutrophils (PMN). Scatchard analysis for binding experiments using [ 3 H]S-145, a specific TXA 2 /prostaglandin H 2 (PGH 2 ) receptor antagonist, revealed the existence of a single class of binding sites ( K d = 83.0 ± 2.8 nM, B max = 113.0 ± 3.1 fmol/2·10 6 cells) in human PMN. Upon stimulation with a combination of U46619, a TXA 2 mimetic agonist, and N -Formylmethionylleucylphenylalanine (FMLP, 1 μM), the synthesis of PAF was detected, although this was not signficantly enhanced by U46619 or FMLP alone. The maximal production of PAF as well as the maximal activity of acetyl-CoA acetyltransferase was observed at approx. 20 min after addition of both stimuli. The effects of U46619 plus FMLP on PAF synthesis showed dose dependence to different concentrations of U46619 (0.1–10 μM), and were completely inhibited by S-145. Contrarily, no significant amounts of LTB 4 were detected by radioimmunoassay during the stimulation with U46619 and FMLP. These results suggest that TXA 2 and FMLP synergistically activate human PMN to induce PAF synthesis and this effect of TXA 2 is mediated through its specific receptor.
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Synergistic effect of throm☐ane A2 and N-Formylmethionylleucylphenylalanine on platelet-activating factor synthesis in human polymorphonuclear neutrophils
Biochimica et Biophysica Acta, 1991Co-Authors: Junji Kishino, Kohji Hanasaki, Toshiyuki Kato, Hitoshi AritaAbstract:Abstract The effects of throm☐ane A 2 (TXA 2 ) on the synthesis of platelet-activating factor (PAF) and leukotriene B 4 (LTB 4 ) were studied using human polymorphonuclear neutrophils (PMN). Scatchard analysis for binding experiments using [ 3 H]S-145, a specific TXA 2 /prostaglandin H 2 (PGH 2 ) receptor antagonist, revealed the existence of a single class of binding sites ( K d = 83.0 ± 2.8 nM, B max = 113.0 ± 3.1 fmol/2·10 6 cells) in human PMN. Upon stimulation with a combination of U46619, a TXA 2 mimetic agonist, and N -Formylmethionylleucylphenylalanine (FMLP, 1 μM), the synthesis of PAF was detected, although this was not signficantly enhanced by U46619 or FMLP alone. The maximal production of PAF as well as the maximal activity of acetyl-CoA acetyltransferase was observed at approx. 20 min after addition of both stimuli. The effects of U46619 plus FMLP on PAF synthesis showed dose dependence to different concentrations of U46619 (0.1–10 μM), and were completely inhibited by S-145. Contrarily, no significant amounts of LTB 4 were detected by radioimmunoassay during the stimulation with U46619 and FMLP. These results suggest that TXA 2 and FMLP synergistically activate human PMN to induce PAF synthesis and this effect of TXA 2 is mediated through its specific receptor.
Stephen J Hardy - One of the best experts on this subject based on the ideXlab platform.
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the neutrophil respiratory burst responses to fatty acids n Formylmethionylleucylphenylalanine and phorbol ester suggest divergent signalling mechanisms
FEBS Journal, 1991Co-Authors: Stephen J Hardy, Brenton S Robinson, A Poulos, Dianne P Harvey, Antonio Ferrante, Andrew W MurrayAbstract:The oxygen-dependent respiratory burst is a key neutrophil function required for the killing of bacteria. However, despite intensive investigation, the molecular events which initiate the respiratory burst remain unclear. Recent reports have suggested the agonist-induced hydrolysis of cellular phosphatidylcholine (PtdCho) by phospholipase D may be an essential requirement for initiating or mediating the respiratory burst. We have investigated the effects of the chemotactic peptide N-Formylmethionylleucylphenylalanine (fMLF), the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) and the polyunsaturated fatty acids arachidonic [20:4 (n-6)] and docosahexaenoic [22:6 (n-3)] acids in light of this hypothesis. Ethanol-inhibited superoxide production in response to 20:4, 22:6 and fMLF, in a dose-dependent fashion, suggesting an involvement of phospholipase D. The phosphatidic-acid phosphohydrolase inhibitor DL-propranolol completely inhibited superoxide production induced by both 20:4 and 22:6, and partially inhibited the response to TPA. In contrast, superoxide production in response to fMLF was increased by propranolol. fMLF and TPA, but not the fatty acids, stimulated phospholipase D as indicated by the accumulation of phosphatidic acid and, in the presence of ethanol, phosphatidylethanol derived from PtdCho. Extracellular Ca2+ was found to be an essential requirement for fMLF-induced superoxide production. However, responses to the fatty acids were dramatically enhanced under Ca2+.-free conditions. Responses to TPA were independent of the extracellular Ca2+ concentration. Both fatty acids and fMLF, but not TPA, mobilised Ca2+ from intracellular stores, a response insensitive to the effects of both ethanol and propranolol. These results show that, unlike fMLF and TPA, the fatty acids do not cause hydrolysis of PtdCho by phospholipase D. However, the data indirectly suggests that the fatty acids may initiate the phospholipase-d-catalysed hydrolysis of phospholipids other than PtdCho.