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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-

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


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