CYCLIC STRETCH OF AIRWAY EPITHELIUM INHIBITS PROSTANOID SYNTHESIS

Airway epithelial cells (AEC) metabolize arachidonic acid (AA) to biol ogically active eicosanoids, which contribute to regulation of airway smooth muscle tone and inflammatory responses. Although in vivo the ai rways undergo cyclical stretching during ventilation, the effect of cy clic stretch on airway epithelial AA metabolism is unknown. In this st udy, cat and human AEC were grown on flexible membranes and were subje cted to cyclic stretch using the Flexercell strain unit. Cyclic stretc h downregulated synthesis of prostaglandin (PG) E-2, PGI(2), and throm boxane Az by both cell types in a frequency-dependent manner. The perc ent inhibition of prostanoid synthesis in both cell types ranged from 53 +/- 7 to 75 +/- 8% (SE; n = 4 and 5, respectively). Treatment of ca t AEC with exogenous AA (10 mu g/ml) had no effect on the stretch-indu ced inhibition of PGE(2) synthesis, whereas treatment with exogenous P GH(2) (10 mu g/ml) overcame the stretch-induced decrease in PGE(2) pro duction. These results indicate that stretch inhibits prostanoid synth esis by inactivating cyclooxygenase. When cells were pretreated with t he antioxidants catalase (100 mu g/ml, 150 U/ml) and N-acetylcysteine (1 mM), there was a partial recovery of eicosanoid production, suggest ing that cyclic stretch-induced inactivation of cyclooxygenase is oxid ant mediated. These results may have important implications for inflam matory diseases in which airway mechanics are altered.