Binding to leukocytes and induction of TNF alpha production involve different sites within the lipid-A region of LPS-like molecules.
The induction of TNF alpha synthesis in whole blood culture assay and isolated peripheral blood mononuclear cells was investigated, using LPS from Klebsiella pneumoniae and two water-soluble 34 kDa derivatives designed as acylpolygalactoside (APG) and EFA-APG, an APG molecule bearing two additional ester-linked fatty acids. Both APG and EFA-APG bind to monocytes by specific ligand receptor interaction but only EFA-APG could induce TNF alpha synthesis. It is concluded that ester-linked fatty acids are not involved in LPS binding to the cell surface, but play a critical role in the triggering of cellular responses.
Mey
A
A
Laboratoire d'Immunologie, INSERM U80 UCBL, Hôpital E. Herriot, Lyon, France.
Hmama
Z
Z
Normier
G
G
Binz
H
H
Revillard
J P
JP
D002240:Carbohydrate Sequence; D007962:Leukocytes / Q000378:metabolism*; D008050:Lipid A / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha