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

F. C. McIntire, M. P. Hargie, J. R. Schenck, R. A. Finley, H. W. Sievert, E. T. Rietschel, D. L. Rosenstreich

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Abstract

Lipopolysaccharide (LPS) 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 2x10 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 moiety of SPLPS may not be necessary for its immunologic adjuvant effect.

Original languageEnglish (US)
Pages (from-to)674-678
Number of pages5
JournalJournal of Immunology
Volume117
Issue number2
StatePublished - Dec 1 1976
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    McIntire, F. C., Hargie, M. P., Schenck, J. R., Finley, R. A., Sievert, H. W., Rietschel, E. T., & Rosenstreich, D. L. (1976). Biologic properties of nontoxic derivatives of a lipopolysaccharide from Escherichia coli K235. Journal of Immunology, 117(2), 674-678.