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.