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Roles of leukotrienes in two rat allergic inflammatory models; IgE-mediated and IgG-antigen complex-induced pleurisies
Authors:Kunio Tanaka  Akinori Ueno  Makoto Katori
Institution:1. Department of Neurology, Medical Faculty, Otto-von-Guericke University, Magdeburg 39120, Germany;2. Department of Haematology and Oncology, Otto-von-Guericke University, Magdeburg 39120, Germany;3. Kyverna Therapeutics, Emeryville, CA, USA;4. Department of Neurology, Ruhr University Bochum, Bochum, Germany;5. Department of Haematology and Oncology, Ruhr University Bochum, Bochum, Germany;6. Department of Rheumatology, Friedrich-Alexander-University, Erlangen, Germany;1. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA;2. Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy;3. Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA, USA;4. Department of Clinical Sciences, Section for Psychiatry, Lund University, Lund, Sweden;5. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA;6. James J. Peters Veterans Affairs Medical Center, New York, NY, USA;7. Department of Psychiatry, New York University, New York, NY, USA;8. Steven and Alexandra Cohen Center for Posttraumatic Stress and TBI, New York, NY, USA;9. Department of OB/GYN and Reproductive Science, University of California San Francisco, San Francisco, CA, USA;1. Département d′informatique et de génie logiciel, Université Laval, Québec, Canada;2. Univ Lyon, UJM-Saint-Etienne, CNRS, IOGS, Laboratoire Hubert Curien UMR 5516, F-42023, Saint-Etienne, France;3. Aix Marseille University, CNRS, Centrale Marseille, LIF, QARMA, Marseille, France;4. Coveo Solutions Inc., Québec, Canada
Abstract:Rat IgE pleurisy was induced by the injection of dinitrophenol-conjugated bovine serum albumin (DNP-BSA) 48 hours after the intrapleural injection of rat anti-DNP-IgE serum. IgG-BSA complex pleurisy was also induced by the intrapleural injection of IgG-BSA complexes produced at the optimum ratio . Plasma exudation was markedly increased in the first 20 minutes, but not observed thereafter, in IgE pleurisy, whereas marked plasma exudation in the first 20 minutes was followed by weak exudation at three and five hours in IgG-BSA complex pleurisy. Leukotrienes (LTs) E4 (100 ng/rat), D4 (32) and B4 (16) were detected on HPLC in the pleural exudate in the first 20 minutes of IgG-BSA complex pleurisy, but less (9 ng/rat) LTE4 alone was detected in the five-hour exudate. The first 20-minute pleural exudate contained 13 ng/rat of LTE4 in IgE pleurisy. The plasma exudation for the initial 20 minutes in IgE pleurisy was completely inhibited by simultaneous treatment of rats with pyrilamine (2.5 mg/kg, i.p.) and methysergide (3 mg/kg, i.p.), as it was in compound 48/80-induced pleurisy. In IgG-BSA complex pleurisy, 90% of the pleural exudate for the first 20 minutes was inhibited by the same treatment, and the rest was completely suppressed by simultaneous treatment with an intrapleural injection of AA-1777, a selective 5-lipoxygenase inhibitor. AA-1777 alone did not reduce the plasma exudation significantly. The 5-lipoxygenase inhibitor was also very effective in reducing the migrating numbers of polymorphonuclear and mononuclear leukocytes to half, without affecting the eosinophils or mast cells.
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