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Prostaglandin EP receptor agonists differentially modulate aspirin-induced generation of 15-HETE in aspirin-sensitive asthmatics
S266 Abstracts
Prostaglandin EP Receptor Agonists Differentially Modulate Aspirin-Induced Generation of 15-HETE in Aspirin-Sensitive Asthmatics M. L. Kowalski1, A. Ptasinska1, M. Jedrzejczak1, B. Bienkiewicz1, M. Borowiec1, L. DuBuske2; 1Department of Allergy and Clinical Immunology, Medical University of Lodz, Lodz, POLAND, 2The Immunology Research Institute of New England, Boston, MA. RATIONALE: Aspirin triggers generation of 15-hydroxyeicosaterraenoic acid (15-HETE) in peripheral blood leukocytes from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The aim of this study was to determine the effect of prostaglandin EP receptor agonists (misoprostol and sulprostone) on aspirin-induced 15HETE generation. METHODS: Peripheral blood leukocytes (PBLs) were isolated from AS and AT patients with asthma, and the 15-HETE release into the cell supernatant was measured with a specific immunoassay (Assay Design, MA). RESULTS: Incubation of PBLs from AS asthmatics with 200µM of lysine-aspirin significantly increased generation of 15-HETE (mean increase +260%) but lysine-aspirin did not affect 15-HETE generation in PBLs from AT asthmatics. Preincubation of cells with misoprostol or sulprostone did not affect basal 15-HETE in AS or AT patients. However, both misoprostol and sulprostone inhibited in a dose-dependent manner the ASA-induced increase in 15-HETE generation in AS asthmatics (maximal inhibition being 89% and 80% after misoprostol and sulprostone respectively). In contrast in AT patients preincubation of PBLs with misoprostol or sulprostone resulted in a significant increase in generation of 15-HETE after addition of 200µM lysine-aspirin. The maximal increase of 15-HETE generation was observed with 10 µg/ml of misoprostol or sulprostone (+73% and +86% respectively). CONCLUSIONS: Our data suggest that aspirin-triggered 15-HETE release is differentially regulated by prostaglandin EP receptors in PBLs from AS and AT asthmatics. Funding: The Polish State Committee for Scientific Research
957
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
TUESDAY
Prostaglandin EP Receptor Agonists Differentially Modulate Aspirin-Induced Generation of 15-HETE in Aspirin-Sensitive Asthmatics M. L. Kowalski1, A. Ptasinska1, M. Jedrzejczak1, B. Bienkiewicz1, M. Borowiec1, L. DuBuske2; 1Department of Allergy and Clinical Immunology, Medical University of Lodz, Lodz, POLAND, 2The Immunology Research Institute of New England, Boston, MA. RATIONALE: Aspirin triggers generation of 15-hydroxyeicosaterraenoic acid (15-HETE) in peripheral blood leukocytes from aspirin-sensitive (AS) but not aspirin-tolerant (AT) patients with asthma/rhinosinusitis. The aim of this study was to determine the effect of prostaglandin EP receptor agonists (misoprostol and sulprostone) on aspirin-induced 15HETE generation. METHODS: Peripheral blood leukocytes (PBLs) were isolated from AS and AT patients with asthma, and the 15-HETE release into the cell supernatant was measured with a specific immunoassay (Assay Design, MA). RESULTS: Incubation of PBLs from AS asthmatics with 200µM of lysine-aspirin significantly increased generation of 15-HETE (mean increase +260%) but lysine-aspirin did not affect 15-HETE generation in PBLs from AT asthmatics. Preincubation of cells with misoprostol or sulprostone did not affect basal 15-HETE in AS or AT patients. However, both misoprostol and sulprostone inhibited in a dose-dependent manner the ASA-induced increase in 15-HETE generation in AS asthmatics (maximal inhibition being 89% and 80% after misoprostol and sulprostone respectively). In contrast in AT patients preincubation of PBLs with misoprostol or sulprostone resulted in a significant increase in generation of 15-HETE after addition of 200µM lysine-aspirin. The maximal increase of 15-HETE generation was observed with 10 µg/ml of misoprostol or sulprostone (+73% and +86% respectively). CONCLUSIONS: Our data suggest that aspirin-triggered 15-HETE release is differentially regulated by prostaglandin EP receptors in PBLs from AS and AT asthmatics. Funding: The Polish State Committee for Scientific Research
957
J ALLERGY CLIN IMMUNOL FEBRUARY 2004
TUESDAY