Endothelin-1 has a priming effect on production of superoxide anion by alveolar macrophages: Its possible correlation with bronchopulmonary dysplasia

The purpose of this study was to clarify the role of endothelin (ET)-1 in the development of bronchopulmonary dysplasia (BPD), Tracheal aspirates were obtained from 27 newborn babies with respiratory distress (13 with BPD and 14 without BPD) who were mechanically ventilated. Production of superoxide anion (O-2(-)) by rabbit alveolar macrophages was determined by preincubation with the tracheal aspirate supenatant (TAS) and stimulation with phorbol myristate acetate (PMA). O-2(-) production was demonstrated only when PMA was added to the experimental system and was enhanced with TAS of infants who later developed BPD compared with TAS from infants without BPD. The effects of ET-1 and ET-3 on O, production and the blockade by anti-ET-1 antibody and BQ123 (ET A receptor antagonist) were also examined. The enhancing effect was blocked by either anti-ET-1 antibody or BQ123, PMA-stimulated production of O-2(-) increased when cells were preincubated with several doses of ET-1 (5 x 10(-13) to 2 x 10(-12) M), whereas ET-3 was without effect. TAS contained significant amounts of immunoreactive ET-1, and there was a close positive correlation (r = 0.764) between the activity of O-2(-) production and immunoreactive ET-1 levels in TAS samples. These results may be interpreted to indicate that ET-1 synthesized by and secreted from tracheal epithelial cells and/or alveolar macrophages has a priming effect on alveolar macrophages to produce O-2(-) thus possibly contributing to the development of BPD.