title: A small key unlocks a heavy door: The essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies.
abstract: The molecular basis involving adsorption of pulmonary surfactant at the respiratory air-liquid interface and the specific roles of the surfactant proteins SP-B and SP-C in this process have not been completely resolved. The reasons might be found in the largely unknown structural assembly in which surfactant lipids and proteins are released from alveolar type II cells, and the difficulties to sample, manipulate and visualize the adsorption of these micron-sized particles at an air-liquid interface under appropriate physiological conditions. Here, we introduce several approaches to overcome these problems. First, by immunofluorescence we could demonstrate the presence of SP-B and SP-C on the surface of exocytosed surfactant particles. Second, by sampling the released particles and probing their adsorptive capacity we could demonstrate a remarkably high rate of interfacial adsorption, whose rate and extent was dramatically affected by treatment with antibodies against SP-B and SP-C. The effect of both antibodies was additive and specific. Third, direct microscopy of an inverted air-liquid interface revealed that the blocking effect is due to a stabilization of the released particles when contacting the air-liquid interface, precluding their transformation and the formation of surface films. We conclude that SP-B and SP-C are acting as essential, preformed molecular keys in the initial stages of surfactant unpacking and surface film formation. We further propose that surfactant activation might be transduced by a conformational change of the surfactant proteins upon contact with surface forces acting on the air-liquid interface.
authors.affiliation: Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany; Department of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria. Electronic address: Nina.Hobi@uni-ulm.de.
authors.forename: Nina
authors.initials: N
authors.lastname: Hobi
authors.affiliation: Department of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Giolai
authors.affiliation: Department of Biochemistry, Faculty of Biology, and Hospital 12 Octubre Research Institute, Universidad Complutense, Jose Antonio Novais 2, 28040 Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Olmeda
authors.affiliation: Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Pika
authors.initials: P
authors.lastname: Miklavc
authors.affiliation: Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Edward
authors.initials: E
authors.lastname: Felder
authors.affiliation: Central Facility for Electron Microscopy, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Walther
authors.affiliation: Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Dietl
authors.affiliation: Institute of General Physiology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Frick
authors.affiliation: Department of Biochemistry, Faculty of Biology, and Hospital 12 Octubre Research Institute, Universidad Complutense, Jose Antonio Novais 2, 28040 Madrid, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Pérez-Gil
authors.affiliation: Department of Physiology and Medical Physics, Division of Physiology, Medical University of Innsbruck, Schöpfstraße 41, 6020 Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haller
mesh_terms: D000327:Adsorption; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001896:Boron Compounds; D002478:Cells, Cultured; D005089:Exocytosis; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D057927:Hydrophobic and Hydrophilic Interactions; D018613:Microscopy, Confocal; D015388:Organelles / Q000187:drug effects / Q000378:metabolism; D037701:Pulmonary Surfactant-Associated Protein B / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D037721:Pulmonary Surfactant-Associated Protein C / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D011663:Pulmonary Surfactants / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013500:Surface Tension
chemical_list: C560998:BODIPY-PC; D001896:Boron Compounds; D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants
keywords: ARDS; Compliance; Lamellar body; Lung injury; Surface tension