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 LP S from Klebsiella pneumoniae and two water-soluble 34 kDa derivatives designed as acylpolygalactoside (APG) and EFA-APG, an APG molecule bea ring two additional ester-linked fatty acids. Both APG and EFA-APG bin d to monocytes by specific ligand receptor interaction but only EFA-AP G could induce TNF alpha synthesis. It is concluded that ester-linked fatty acids are not involved in LPS binding to the cell surface, but p lay a critical role in the triggering of cellular responses.