The highly packed and dehydrated structure of preformed unexposed human pulmonary surfactant isolated from amniotic fluid

By coating the alveolar air-liquid interface, lung surfactant overwhelms surface tension forces that, otherwise, would hinder the lifetime effort of breathing. Years of research have provided a picture of how highly hydrophobic and specialized proteins in surfactant promote rapid and efficient formation of phospholipid-based complex three-dimensional films at the respiratory surface, highly stable under the demanding breathing mechanics. However, recent evidence suggests that the structure and performance of surfactant typically isolated from bronchoalveolar lung lavages may be far from that of nascent, still unused, surfactant as freshly secreted by type II pneumocytes into the alveolar airspaces. In the present work, we report the isolation of lung surfactant from human amniotic fluid (amniotic fluid surfactant, AFS) and a detailed description of its composition, structure, and surface activity in comparison to a natural surfactant (NS) purified from porcine bronchoalveolar lavages. We observe that the lipid/protein complexes in AFS exhibit a substantially higher lipid packing and dehydration than in NS. AFS shows melting transitions at higher temperatures than NS and a conspicuous presence of nonlamellar phases. The surface activity of AFS is not only comparable with that of NS under physiologically meaningful conditions but displays significantly higher resistance to inhibition by serum or meconium, agents that inactivate surfactant in the context of severe respiratory pathologies. We propose that AFS may be the optimal model to study the molecular mechanisms sustaining pulmonary surfactant performance in health and disease, and the reference material to develop improved therapeutic surfactant preparations to treat yet unresolved respiratory pathologies.

Automated summary

Lung surfactant plays a crucial role in overcoming surface tension forces and facilitating breathing. The structure and performance of surfactant isolated from bronchoalveolar lung lavages may differ from freshly secreted surfactant. In this study, lung surfactant isolated from human amniotic fluid (AFS) was compared to natural surfactant purified from porcine bronchoalveolar lavages. AFS exhibited higher lipid packing and dehydration, melting transitions at higher temperatures, and higher resistance to inhibition, making it a promising model to study surfactant performance and develop therapeutic surfactant preparations.