INTERACTION OF TRANSFERRIN SATURATED WITH IRON WITH LUNG SURFACTANT IN RESPIRATORY-FAILURE

Proteins that decrease the surface activity of surfactant accumulate i n epithelial lining fluid in respiratory failure. The aim of this stud y was to isolate a surfactant inhibitor from the airways of rabbits in acute respiratory failure induced by bronchoalveolar lavage (BAL). Th is inhibitor was identified as being transferrin (TF). Unlike serum TF , TF recovered in respiratory failure was saturated with iron (Fe3+-TF ). Fe3+-TF decreased the surface activity of normal surfactant in vitr o, whereas iron-free TF had no effect. In the presence of H2O2 and a r educing agent, Fe3+-TF inactivated the surfactant complex: the surface adsorption rate was decreased, immunoreactive surfactant protein A wa s decreased, and malondialdehyde was formed. The acute effects of Fe3-TF and iron-free TF applied to the airways were studied in animal mod els. In respiratory failure induced by BAL, Fe3+-TF deteriorated respi ratory failure, whereas iron-free TF had no effect. In respiratory fai lure induced by hyperoxia for 48 h, administration of iron-free TF ame liorated the respiratory failure and improved the surface activity in BAL. We propose that Fe3+-TF accumulating in epi thelial lining fluid during lung damage contributes to surfactant inhibition and promotes t he formation of free radicals that inactivate the surfactant system.