Protein-lipid interactions and surface activity in the pulmonary surfactant system.
Pulmonary surfactant is a lipid-protein complex, synthesized and secreted by the respiratory epithelium of lungs to the alveolar spaces, whose main function is to reduce the surface tension at the air-liquid interface to minimize the work of breathing. The activity of surfactant at the alveoli involves three main processes: (i) transfer of surface active molecules from the aqueous hypophase into the interface, (ii) surface tension reduction to values close to 0 mN/m during compression at expiration and (iii) re-extension of the surface active film upon expansion at inspiration. Phospholipids are the main surface active components of pulmonary surfactant, but the dynamic behaviour of phospholipids along the breathing cycle requires the necessary participation of some specific surfactant associated proteins. The present review summarizes the current knowledge on the structure, disposition and lipid-protein interactions of the hydrophobic surfactant proteins SP-B and SP-C, the two main actors participating in the surface properties of pulmonary surfactant. Some of the methodologies currently used to evaluate the surface activity of the proteins in lipid-protein surfactant preparations are also revised. Working models for the potential molecular mechanism of SP-B and SP-C are finally discussed. SP-B might act in surfactant as a sort of amphipathic tag, directing the lipid-protein complexes to insert and re-insert very efficiently into the air-liquid interface along successive breathing cycles. SP-C could be essential to maintain association of lipid-protein complexes with the interface at the highest compressed states, at the end of exhalation. The understanding of the mechanisms of action of these proteins is critical to approach the design and development of new clinical surfactant preparations for therapeutical applications.
Serrano
Alicia G
AG
Departamento de Bioquímica y Biología Molecular I, Facultad de Biología, Universidad Complutense, Jose Antonio Novais 2, Madrid, Spain.
Pérez-Gil
Jesús
J
D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism; D008168:Lung / Q000378:metabolism*; D008561:Membrane Fusion; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000737:chemistry / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C / Q000737:chemistry / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000378:metabolism; D013500:Surface Tension
D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants