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Biologic properties of nontoxic derivatives of a lipopolysaccharide from Escherichia coli K235.

Abstract
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.
AuthorsF C McIntire, M P Hargie, J R Schenck, R A Finley, H W Sievert, E T Rietschel, D L Rosenstreich
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 117 Issue 2 Pg. 674-8 (Aug 1976) ISSN: 0022-1767 [Print] UNITED STATES
PMID781135 (Publication Type: Journal Article)
Chemical References
  • Adjuvants, Immunologic
  • Endotoxins
  • Interferon Inducers
  • Lipopolysaccharides
  • Mitogens
  • Phthalic Acids
  • Polysaccharides, Bacterial
  • Pyrogens
  • Succinates
Topics
  • Adjuvants, Immunologic
  • Animals
  • Antigen-Antibody Reactions
  • Endotoxins
  • Escherichia coli (immunology)
  • Interferon Inducers
  • Lipopolysaccharides (isolation & purification, physiology)
  • Mice
  • Mitogens
  • Phthalic Acids
  • Polysaccharides, Bacterial (physiology)
  • Pyrogens
  • Rabbits
  • Rats
  • Shwartzman Phenomenon
  • Succinates

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