Physical state and biological activity of lipopolysaccharides. Toxicity and immunogenicity of the lipid A component.

Abstract

Bacterial lipopolysaccharides are negatively charged macromolecules due to the presence of phosphate, pyrophosphate and carboxyl groups. When isolated from bacteria, they are obtained in salt form with metal cations and basic amines. Removal of these ionically bound substances by electrodialysis leads to acidic lipopolysaccharides which on neutralizing with different bases, preparations are obtained which show distinct differences in their physico-chemical properties and in their biological activity. Soluble lipopolysaccharides interact with complement leading to loss of hemolytic activity. This property is embedded in the lipid A part of the molecule and is expressed only when the lipopolysaccharide is present in a favourable particle size. Nevertheless, a number of lipopolysaccharides exists, which, regardless of their particle size do not interact with complement. Lipid A is the part of the molecule responsible for endotoxicity. This was demonstrated by employing solubilized lipid A in complex form with BSA. Soluble lipid A/BSA complexes proved highly toxic for mice and pyrogenic in rabbits, and express many biological activities exhibited by intact lipopolysaccharides. Lipid A, when exposed on the bacterial cell-surface acts as a powerful immunogen, giving rise to the production of specific anti-lipid A antibodies that interact with the lipid A obtained from lipopolysaccharides that are otherwise distinct in their O-serological specificity. Anti-lipid A antibodies occur naturally in the serum of many animals and humans. The biological significance of anti-lipid A antibodies is discussed.