Symposium on bacterial endotoxins. I. Relationship of chemical composition to biological activity.

Although endotoxins have been studied intensively by competent investigators during the past several decades, exact relationships between chemical constitution and capacity to evoke characteristic reactions in mammals remain largely unknown. As ordinarily isolated, endotoxins are complexes of lipid, polysaccharide, and protein or peptide-like substances; but the proportions of each have been found to vary with the method of isolation. The question arose whether all of these components were essential to the properties ordinarily referred to as "endotoxic." Morgan and Partridge (9) found the protein moiety necessary to endotoxic potency. However, Westphal and Lideritz (19), Webster et al. (16), and Landy et al. (7) demonstrated that an essentially protein-free lipopolysaccharide retained the ability to stimulate all the characteristic physiological effects, thus rendering an important role for protein unlikely. This conclusion is supported by our own findings (12). Boivin and Mesrobeanu (1) and Freeman (3) demonstrated that hydrolysis of endotoxin with dilute acetic acid destroyed antigenicity in vivo and most of the endotoxic potency, leaving the serologically specific polysaccharide hapten and a lipid component which was extractable in chloroform. Lipids freed from endotoxins by hydrolysis with acid were originally thought to be physiologically inactive, but Westphal and Luderitz (19) showed that certain of them retained at least some endotoxic properties. The material which they called Lipoid A (lipid A) appeared as chloroformor pyridine-soluble substance in the product of hydrolysis of endotoxin with 1 N HCL. They found that redispersion of lipid A in aqueous menstruum by detergents or