Conversion of lipopolysaccharides to molecular aggregates with reduced subunit heterogeneity: demonstration of LPS-responsiveness in "endotoxin-unresponsive" C3H/HeJ splenocytes.

Lipopolysaccharides (LPS) of homogeneous monomeric composition were prepared by gel filtration chromatography of detergent-dissociated LPS from the smooth strain of E. coli 055:B5. Splenocyte mitogenic activity of reassociated column fractions and fraction pools is markedly dependent upon the ratio of O-antigen polysaccharide to lipid A. The activity of the homogeneous LPS in eliciting spleen cell responses varied by approximately three orders of magnitude. One of the fraction pools rich in lipid A (which contains only a trace of O-antigen polysaccharide) induces a spleen cell proliferative response in C3H/HeJ "LPS-nonresponder" spleen cells. This mitogenic activity is not present in either unfractionated LPS or O-antigen-rich fractions. These latter findings indicate LPS macromolecular aggregates of the appropriate physicochemical structure have the capacity to elicit C3H/HeJ spleen cell proliferative responses.