International Journal of Molecular Sciences Review Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis Olga Cañadas 1,2,Bárbara Olmeda 1,2, Alejandro Alonso 1,2 and Jesús Pérez-Gil 1,2,* 1 Departament of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040 Madrid, Spain;
[email protected] (O.C.);
[email protected] (B.O.);
[email protected] (A.A.) 2 Research Institut “Hospital Doce de Octubre (imasdoce)”, 28040 Madrid, Spain * Correspondence:
[email protected]; Tel.: +34-913944994 Received: 9 May 2020; Accepted: 22 May 2020; Published: 25 May 2020 Abstract: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface. Keywords: pulmonary surfactant film; surfactant metabolism; surface tension; respiratory air–liquid interface; inflammation; antimicrobial activity; apoptosis; efferocytosis; tissue repair 1.