Arachidonic acid and eicosapentaenoic acid stimulate type II pneumocyte surfactant secretion

Arachidonic acid and its leukotriene metabolites have been shown to stimulate surfactant secretion by alveolar type II cells. The present study was undertaken to determine the effects of various unsaturated fatty acids, including eicosapentaenoic acid, on surfactant secretion. Surfactant secretion was expressed as the percent of [3H]choline-derived phospholipids released into culture medium by type II pneumocytes of adult rats. Consistent with the earlier findings, arachidonic acid stimulated secretion in a concentration-dependent fashion (3.5-21 microM), doubling baseline secretion at 21 microM. Eicosapentaenoic acid was found to be equally effective as arachidonic acid in stimulating secretion. A comparison with palmitic, oleic and linoleic acids revealed that highly unsaturated fatty acids stimulated secretion to the greatest extent. This was supported by a positive correlation between degree of unsaturation (i.e., 0, 1, 2, 4 and 5 double bonds) and stimulation of surfactant secretion. In the present study, exogenous leukotriene E4 (10(-13)-10(-6) did not stimulate surfactant secretion. Neither nordihydroguairetic acid (0.1 microM) nor indomethacin (0.1 microM) affected arachidonic acid-stimulated secretion. The stimulatory effects of arachidonic acid and eicosapentaenoic acid on surfactant secretion were related to the highly unsaturated nature of the fatty acids and were not mediated by increased levels of cyclic adenosine monophosphate or calcium.