Synthetic peptides representing the N-terminal segment of surfactant protein C modulate LPS-stimulated TNF-alpha production by macrophages.
Innate Immun
; 15(1): 53-62, 2009 Feb.
Article
em En
| MEDLINE
| ID: mdl-19201825
ABSTRACT
Surfactant protein C (SP-C) consists of a hydrophobic alpha-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-alpha by these cells. These effects were reversed in the presence of serum; the analogs reduced the production of TNF-alpha 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Lipopolissacarídeos
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Fator de Necrose Tumoral alfa
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Macrófagos Peritoneais
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article