Cellular antiendotoxin activities of lung surfactant protein C in lipid vesicles.
The respiratory system is continuously exposed to airborne particles containing lipopolysaccharide. Our laboratory established previously that the hydrophobic surfactant protein C (SP-C) binds to lipopolysaccharide and to one of its cellular receptors, CD14. Here we examined the influence of SP-C, and of a synthetic analog, on some cellular in vitro effects of lipopolysaccharide. When associated with vesicles of dipalmitoylphosphatidylcholine, SP-C inhibits the binding of a tritium-labeled lipopolysaccharide to the macrophage cell line RAW 264.7. Under similar conditions of presentation, SP-C inhibits the mitogenic effect of lipopolysaccharide on mouse splenocytes, and inhibits the lipopolysaccharide-induced production of tumor necrosis factor-alpha by peritoneal and alveolar macrophages, and of nitric oxide by RAW 264.7 cells. In contrast, tumor necrosis factor-alpha production induced by a lipopeptide, and nitric oxide production induced by picolinic acid, were not affected by SP-C. The lipopolysaccharide-binding capacity of SP-C is resistant to peroxynitrite, a known mediator of acute lung injury formed by reaction of nitric oxide with superoxide anions. These results indicate that SP-C may play a role in lung defense; SP-C resists degradation under inflammatory conditions and traps lipopolysaccharide, preventing it from inducing production of noxious mediators in alveolar cells.
Augusto
Luis A
LA
Laboratory of Nitrogen Oxides Inflammation and Immunity, UMR-8619, Université de Paris-Sud, Orsay, France.
Synguelakis
Monique
M
Espinassous
Quentin
Q
Lepoivre
Michel
M
Johansson
Jan
J
Chaby
Richard
R
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000187:drug effects*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D016166:Free Radical Scavengers / Q000032:analysis; D066298:In Vitro Techniques; D018950:Lipopolysaccharide Receptors / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis; D037721:Pulmonary Surfactant-Associated Protein C / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000970:Antineoplastic Agents; D004731:Endotoxins; D016166:Free Radical Scavengers; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide