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Activation of calcium‐independent phospholipase A 2 β increases platelet activating factor and PGI 2 production in cardiac endothelial cells
Author(s) -
Sharma Janhavi S,
McHowat Jane
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.590.3
Subject(s) - thrombin , arachidonic acid , stimulation , prostacyclin , medicine , tryptase , endocrinology , chemistry , phospholipase a2 , platelet activation , phospholipase , bradykinin , phospholipase c , platelet , calcium , platelet activating factor , receptor , biochemistry , biology , enzyme , immunology , mast cell
The endothelium is a critical barrier between the circulation and underlying tissues. We have previously shown that activation of protease‐activated receptor‐1 (PAR‐1) and PAR‐2 on the surface of endothelial cells (EC) by tryptase or thrombin increases calcium‐independent phospholipase A 2 β (iPLA 2 β) activity resulting in the production of multiple membrane phospholipid‐derived inflammatory metabolites. We isolated EC from hearts of iPLA 2 β knockout (KO) and wild type (WT) mice and measured arachidonic acid (AA), prostacyclin (PGI 2 ) and platelet‐activating factor (PAF) production in response to PAR stimulation. Thrombin stimulation (0.1 IU/ml) of WT EC rapidly increased AA (0.89 + 0.07 to 2.23+0.13%) and PGI 2 release (75.0 + 2.8 to 133.7 + 3.4 pg/ml) and increased PAF production (1216 + 79 to 2308 + 259 dpm). Similar increases were observed with tryptase (20 ng/ml) stimulation. Thrombin and tryptase‐stimulated responses were inhibited by pretreatment of WT EC with S‐bromoenol lactone (( S )‐BEL, 5μM, 10mins), which selectively inhibits iPLA 2 β. Thrombin or tryptase stimulation of iPLA 2 β KO EC demonstrated no significant increase in PAF production and inhibited AA and PGI 2 release. These results indicate that iPLA 2 β is the predominant isoform in EC and could contribute to inflammation via PGI 2 and PAF production.