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Infection and Immunity, January 2003, p. 61-67, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.61-67.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Interaction of Pulmonary Surfactant Protein C with CD14 and Lipopolysaccharide

Luis A. Augusto,1 Monique Synguelakis,1 Jan Johansson,2 Thierry Pedron,3 Robert Girard,4 and Richard Chaby1*

Endotoxin Group, National Center for Scientific Research, UMR-8619, University of Paris-Sud, Orsay,1 Pathogénie Microbienne Moléculaire, INSERM U389,3 Lymphocyte Development, National Center for Scientific Research, URA-1961, Pasteur Institute, Paris, France,4 Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden2

Received 18 June 2002/ Returned for modification 4 September 2002/ Accepted 11 October 2002

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.


* Corresponding author. Mailing address: Equipe Endotoxines, CNRS, UMR-8619, BÂtiment 430, Université de Paris-Sud, 91405 Orsay Cedex, France. Phone: 33-1 69 15 48 30. Fax: 33-1 69 85 37 15. E-mail: richard.chaby{at}bbmpc.u-psud.fr.

Editor: J. D. Clements


Infection and Immunity, January 2003, p. 61-67, Vol. 71, No. 1
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.1.61-67.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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