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 aspi rates were obtained from 27 newborn babies with respiratory distress ( 13 with BPD and 14 without BPD) who were mechanically ventilated. Prod uction of superoxide anion (O-2(-)) by rabbit alveolar macrophages was determined by preincubation with the tracheal aspirate supenatant (TA S) and stimulation with phorbol myristate acetate (PMA). O-2(-) produc tion was demonstrated only when PMA was added to the experimental syst em and was enhanced with TAS of infants who later developed BPD compar ed 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 r eceptor antagonist) were also examined. The enhancing effect was block ed by either anti-ET-1 antibody or BQ123, PMA-stimulated production of O-2(-) increased when cells were preincubated with several doses of E T-1 (5 x 10(-13) to 2 x 10(-12) M), whereas ET-3 was without effect. T AS 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 res ults may be interpreted to indicate that ET-1 synthesized by and secre ted from tracheal epithelial cells and/or alveolar macrophages has a p riming effect on alveolar macrophages to produce O-2(-) thus possibly contributing to the development of BPD.