title: Pneumocytes Assemble Lung Surfactant as Highly Packed/Dehydrated States with Optimal Surface Activity.
abstract: Pulmonary surfactant (PS) is an essential complex of lipids and specific proteins synthesized in alveolar type II pneumocytes, where it is assembled and stored intracellularly as multilayered organelles known as lamellar bodies (LBs). Once secreted upon physiological stimulation, LBs maintain a densely packed structure in the form of lamellar body-like particles (LBPs), which are efficiently transferred into the alveolar air-water interface, lowering surface tension to avoid lung collapse at end-expiration. In this work, the structural organization of membranes in LBs and LBPs freshly secreted by primary cultures of rat ATII cells has been compared with that of native lung surfactant membranes isolated from porcine bronchoalveolar lavage. PS assembles in LBs as crystalline-like highly ordered structures, with a highly packed and dehydrated state, which is maintained at supraphysiological temperatures. This relatively ordered/packed state is retained in secreted LBPs. The micro- and nanostructural examination of LBPs suggests the existence of high levels of structural complexity in comparison with the material purified from lavages, which may contain partially inactivated or spent structures. Additionally, freshly secreted surfactant LBPs exhibit superior activity when generating interfacial films and a higher intrinsic resistance to inactivating agents, such as serum proteins or meconium. We propose that LBs are assembled as an energy-activated structure competent to form very efficient interfacial films, and that the organization of lipids and proteins and the properties displayed by the films formed by LBPs are likely similar to those established at the alveolar interface and represent the actual functional structure of surfactant as it sustains respiration.
authors.affiliation: Department of Biochemistry, Faculty of Biology, and Hospital 12 Octubre Research Institute, Universidad Complutense, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cerrada
authors.affiliation: Department of Physiology and Medical Physics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haller
authors.affiliation: Department of Biochemistry, Faculty of Biology, and Hospital 12 Octubre Research Institute, Universidad Complutense, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cruz
authors.affiliation: Department of Biochemistry, Faculty of Biology, and Hospital 12 Octubre Research Institute, Universidad Complutense, Madrid, Spain. Electronic address: jperezgil@bio.ucm.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Pérez-Gil
mesh_terms: D000327:Adsorption; D000388:Air; D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D008297:Male; D015388:Organelles / Q000737:chemistry / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D014867:Water / Q000378:metabolism*
chemical_list: D011663:Pulmonary Surfactants; D014867:Water