Interaction of pulmonary surfactant protein C with CD14 and lipopolysaccharide.
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.
Augusto
Luis A
LA
Endotoxin Group, National Center for Scientific Research, UMR-8619, University of Paris-Sud, Orsay, France.
Synguelakis
Monique
M
Johansson
Jan
J
Pedron
Thierry
T
Girard
Robert
R
Chaby
Richard
R
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
D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants