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Synthetic peptides representing the N-terminal segment of surfactant protein C modulate LPS-stimulated TNF- production by macrophages

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Elvira Garcia de Paco

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Quentin Espinassous

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Azucena Gonzalez-Horta

Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Madrid, Spain

Monique Synguelakis

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Jean Kanellopoulos

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Luis Rivas

Centro de Investigaciones Biológicas, CSIC, Madrid, Spain

Richard Chaby

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, UMR-8619 du CNRS, Université de Paris-Sud, Orsay, France

Jesús Perez-Gil

Departamento de Bioquímica y Biología Molecular I, Universidad Complutense de Madrid, Madrid, Spain, jpg{at}bbm1.ucm.es

Surfactant protein C (SP-C) consists of a hydrophobic -helix inserted in pulmonary surfactant membranes, and a more polar N-terminal palmitoylated segment exposed to the aqueous phase. Previously, we showed that SP-C inserted in lipid vesicles interacts with bacterial lipopolysaccharide (LPS) and reduces LPS-elicited responses. As the N-terminal segment of SP-C was the most likely region responsible for these effects, a set of synthetic analogs of this stretch (SPC_(1-13) ) were studied. Binding studies showed that SPC_(1-13) binds LPS to the same extent as porcine SP-C under lipid-free conditions. In the absence of serum, both, palmitoylated and non-palmitoylated analogs enhanced the binding of tritiated LPS to macrophages as well as the LPS-induced production of TNF- by these cells. These effects were reversed in the presence of serum; the analogs reduced the production of TNF- in LPS-stimulated macrophages, probably by interfering with the formation of LPS/CD14/LBP complexes as suggested by analysis of the fluorescence emitted by a FITC derivative of Re-LPS. Our data indicate that water-soluble analogs of the N-terminal segment of SP-C can reduce LPS effects in the presence of serum, and thus might help in the design of new derivatives to fight endotoxic shock and pro-inflammatory events.

Key Words: Inflammation • LBP • LPS • SP-C synthetic peptides • TNF-

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Innate Immunity, Vol. 15, No. 1, 53-62 (2009)
DOI: 10.1177/1753425908100500


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Garcia-Verdugo, I. Articles by Perez-Gil, J. Search for Related Content PubMed PubMed Citation Articles by Garcia-Verdugo, I. Articles by Perez-Gil, J. Social Bookmarking                         What's this?