Biologic properties of nontoxic derivatives of a lipopolysaccharide from Escherichia coli K235.
Lipopolysaccharide (LPS)2 from Escherichia coli K235 was treated with o-phthalic anhydride to obtain a high degree of esterification of available hydroxyl groups, leaving a free carboxyl for each hydroxyl esterified (SPLPS). Although there was no demonstrable loss of fatty acids, this conversion of LPS to a polyanionic molecule altered dramatically the spectrum of biologic properties, most of which are normally attributed to the lipid A (LA) moiety. Mitogenicity for mouse B cells was decreased several hundred-fold; reaction with antibodies to LPS was abolished; pyrogenicity and toxicity were decreased by factors of 10(5) and 10(4); the ability to induce the Shwartzman reaction in rabbits was decreased 500-fold, and the ability to stimulate production of interferon in mice was decreased by more than 2 x 10(3). However, despite the loss of these properties, SPLPS retained the ability to act as an immunologic adjuvant. The nature of the anionic group is important, e.g., sodium succinyl-LPS (SuLPS) is 10-fold more pyrogenic and toxic than sodium phthalyl-LPS (SPLPS). Data on another LPS derivative, from which ester-linked fatty acid residues were removed before phthalylation, suggest that the ester-linked fatty acid groups in the lipid A moeity of SPLPS may not be necessary for its immunologic adjuvant effect.
D000276:Adjuvants, Immunologic; D000818:Animals; D000937:Antigen-Antibody Reactions; D004731:Endotoxins; D004926:Escherichia coli / Q000276:immunology*; D007369:Interferon Inducers; D008070:Lipopolysaccharides / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008934:Mitogens; D010795:Phthalic Acids; D011135:Polysaccharides, Bacterial / Q000502:physiology*; D011749:Pyrogens; D011817:Rabbits; D051381:Rats; D012790:Shwartzman Phenomenon; D013386:Succinates
D000276:Adjuvants, Immunologic; D004731:Endotoxins; D007369:Interferon Inducers; D008070:Lipopolysaccharides; D008934:Mitogens; D010795:Phthalic Acids; D011135:Polysaccharides, Bacterial; D011749:Pyrogens; D013386:Succinates