Inhibition of Cytosolic Phospholipase A2 in Human Neutrophils by Oxatomide
| Autor: | Gianni Marone, Alfonso Oriente, Francescopaolo Granata, Massimo Triggiani, Cecilia Calabrese |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
biology
Immunology Inflammation General Medicine Lipid signaling Granulocyte Pathogenesis chemistry.chemical_compound Mediator Phospholipase A2 medicine.anatomical_structure Biochemistry chemistry medicine biology.protein Immunology and Allergy Arachidonic acid Oxatomide medicine.symptom medicine.drug |
| Zdroj: | International Archives of Allergy and Immunology. 124:367-370 |
| ISSN: | 1423-0097 1018-2438 |
| DOI: | 10.1159/000053760 |
| Popis: | Background: Lipid mediators play a pivotal role in the pathogenesis of allergic and inflammatory reactions. These molecules include metabolites of arachidonic acid (AA) and the group of platelet-activating factor (PAF)-related phospholipids. The initial step in the synthetic pathway of both classes of lipid mediators is catalyzed by members of the phospholipase A2 (PLA2) family. Oxatomide is a histamine H1 receptor antagonist currently used in the treatment of allergic disorders. Preliminary evidence indicates that oxatomide may exert anti-inflammatory activities unrelated to H1 receptor antagonism. Methods: We investigated the effect of oxatomide on lipid mediator production by human neutrophils. Results: Preincubation (15 min, 37°C) of neutrophils with oxatomide (10–100 µM) concentration-dependently inhibited (10–70%) the release of AA induced by the Ca2+ ionophore A23187 (0.5 µM). Oxatomide also comparably inhibited the release of the four major metabolites of AA induced by A23187 (LTB4, 20-OH-LTB4, 20-COOH-LTB4 and 5-HETE). In addition, oxatomide reduced by 60% the production of PAF induced by A23187. The simultaneous inhibition of the production of AA metabolites and PAF suggested that oxatomide could influence the activity of cytosolic PLA2 (cPLA2). To test this hypothesis, we evaluated the functional activity of cPLA2 in neutrophils preincubated with oxatomide. This preincubation inhibited (72 ± 24%) the increase in cPLA2 activity induced by A23187. Conclusions: These results indicate that oxatomide reduces the biosynthesis of lipid mediators in human neutrophils by inhibiting cPLA2. This inhibitory effect of oxatomide may contribute to the anti-inflammatory activity of this drug in allergic diseases. |
| Databáze: | OpenAIRE |
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