Inhibition of cytosolic phospholipase A(2) in human neutrophils by oxatomide

Citation
M. Triggiani et al., Inhibition of cytosolic phospholipase A(2) in human neutrophils by oxatomide, INT A AL IM, 124(1-3), 2001, pp. 367-370
Citations number
22
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY
ISSN journal
1018-2438 → ACNP
Volume
124
Issue
1-3
Year of publication
2001
Pages
367 - 370
Database
ISI
SICI code
1018-2438(200101/03)124:1-3<367:IOCPAI>2.0.ZU;2-J
Abstract
Background Lipid mediators play a pivotal role in the pathogenesis of aller gic and inflammatory reactions. These molecules include metabolites of arac hidonic acid (AA) and the group of platelet-activating factor (PAF) related phospholipids, The initial step in the synthetic pathway of both classes o f lipid mediators is catalyzed by members of the phospholipase A(2) (PLA(2) ) family. Oxatomide is a histamine H-1 receptor antagonist currently used i n the treatment of allergic disorders. Preliminary evidence indicates that oxatomide may exert anti-inflammatory activities unrelated to H1 receptor a ntagonism. Methods: We investigated the effect of oxatomide on lipid mediat or production by human neutrophils. Results: Preincubation (15 min, 37 degr eesC) of neutrophils with oxatomide (10-100 muM) concentration-dependently inhibited (10-70%) the release of AA induced by the Ca2+ ionophore A23187 ( 0.5 muM). 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 PLA(2) (cPLA(2)). To test this hypothesis, we evaluated the functional acti vity of cPLA(2) in neutrophils preincubated with oxatomide, This preincubat ion inhibited (72 +/- 24%) the increase in cPLA(2) activity induced by A231 87. Conclusions: These results indicate that oxatomide reduces the biosynth esis of lipid mediators in human neutrophils by inhibiting cPLA(2). This in hibitory effect of oxatomide may contribute to the anti-inflammatory activi ty of this drug in allergic diseases. Copyright (C) 2001 S. Karger AG, Base l.