Mitogenic activities of lipid A and liposome-associated lipid A: effects of epitope density.

Among eight purified lipid A fractions, there was heterogeneity of mitogenic activity, but the relative activity could not be predicted by limulus amebocyte lysate assay. Analysis of mitogenic activity after the incorporation of lipid A into liposomes demonstrated that epitope density of lipid A was a crucial factor that strongly modulated expression of lipid A. The results suggest that lipid A hydrophobic groups are responsible for mitogenic activity and that the surface accessibility of lipid A hydrophobic groups in membranes may be influenced by epitope density. The data are compared with previous results derived from parallel studies on limulus amebocytes. Both approaches lead to the conclusion that the activities of purified lipid A fractions are heterogeneous and that epitope density is critically important for the expression of biologic activity of membrane-associated lipid A.