PGE 2 release from tryptase‐stimulated rabbit ventricular myocytes is mediated by calcium‐independent phospholipase A 2 γ

Inflammation is associated with several cardiovascular diseases and mast cells have been implicated in many of these, but their precise role remains unclear. We hypothesize that tryptase, a pre formed mast cell mediator, stimulates rabbit ventricular myocyte calcium independent phospholipase A 2 (iPLA 2 ) activity, resulting in increased arachidonic acid and prostaglandin E 2 (PGE 2 ) release. Tryptase stimulation (20 ng/ml) increased iPLA 2 activity after 5 mins (3.56 ± 0.12 to 5.87 ± 0.31 nmol/mg protein/min, n=6, p<0.01). This was accompanied by increased arachidonic acid (1.02 ± 0.12 to 5.02 ± 0.21%, n=6, p<0.01) and PGE 2 release (4.50 ± 0.30 to 16.70 ± 0.59 ng/mg protein, n=8, p<0.01) in stimulated myocytes. To distinguish between different myocardial iPLA 2 isoforms, we pretreated ventricular myocytes with the R‐ and S‐ enantiomers of bromoenol lactone (BEL, 5 μM, 10 mins) to selectively inhibit iPLA 2 γ and β respectively. ( R )‐BEL pretreatment resulted in complete inhibition of tryptase‐stimulated iPLA 2 activity, arachidonic acid and PGE 2 release, suggesting the iPLA 2 γ is activated in response to tryptase. Pretreatment with (S)‐BEL had little effect on tryptase‐stimulated responses. Previous studies suggest that PGE 2 may be cardioprotective. Thus tryptase release from activated mast cells may play a protective role in cardiac inflammation via iPLA 2 γ activation and increased PGE 2 release from myocytes.