Activation of murine spleen cells by lipid A: negative modulation of lipid A mitogenic activity by O-antigen polysaccharide.

We have investigated the regulatory effects of polysaccharide-rich subunits upon lipid A activity with the use of hybrid LPS macromolecules of defined subunit composition. Hybrid LPS were constructed with polysaccharide-rich LPS from Escherichia coli O55:B5 and lipid A-rich LPS from Salmonella minnesota R595 by dissociation of the two parental LPS species to monomeric solutions with deoxycholate, admixing these LPS in various proportions and reassociation into high m.w. LPS hybrid aggregates by removal of the deoxycholate. Isopycnic densities of LPS hybrids were intermediate to those of the two parental LPS species, confirming the formation of true hybrids. Murine spleen cell proliferative responses induced by hybrid LPS macromolecules were also intermediate to those obtained with parental LPS but significantly less than would be anticipated on the basis of total lipid A content. These results demonstrate that the polysaccharide portion of LPS can negatively regulate the expression of lipid A in LPS micellar aggregates.