title: Interaction of pulmonary surfactant protein C with CD14 and lipopolysaccharide.
abstract: In addition to their effects on alveolar surface tension, some components of lung surfactant also have immunological functions. We found recently that the hydrophobic lung surfactant protein SP-C specifically binds to the lipid A region of lipopolysaccharide (LPS). In this study, we show that SP-C also interacts with CD14. Four observations showed cross talk between the three molecules SP-C, LPS, and CD14. (i) Like LBP, SP-C allows the binding of a fluorescent LPS to cells expressing CD14 (the other surfactant components were ineffective). (ii) Recombinant radiolabeled CD14 and SP-C (or a synthetic analog of SP-C) interact in a dose-dependent manner. (iii) LPS blocks the binding of radiolabeled CD14 to SP-C-coated wells. (iv) SP-C enhances the binding of radiolabeled CD14 to LPS-coated wells. These results, obtained with native murine SP-C and with three synthetic analogs, suggest that LPS and CD14 interact with the same region of SP-C and that binding of SP-C modifies the conformation of CD14 or the accessibility of its LPS-binding site, allowing it to bind LPS. This ability of SP-C to interact with the pattern recognition molecule CD14 extends the possible immunological targets of SP-C to a large panel of microorganisms that can enter the airways.
authors.affiliation: Endotoxin Group, National Center for Scientific Research, UMR-8619, University of Paris-Sud, Orsay, France.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Augusto
authors.forename: Monique
authors.initials: M
authors.lastname: Synguelakis
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedron
authors.forename: Robert
authors.initials: R
authors.lastname: Girard
authors.forename: Richard
authors.initials: R
authors.lastname: Chaby
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D037721:Pulmonary Surfactant-Associated Protein C / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011663:Pulmonary Surfactants / Q000378:metabolism*; D019779:Salmonella enterica / Q000378:metabolism
chemical_list: D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants