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. 1993 Oct;61(10):4514–4517. doi: 10.1128/iai.61.10.4514-4517.1993

An artificial glycoconjugate containing the bisphosphorylated glucosamine disaccharide backbone of lipid A binds lipid A monoclonal antibodies.

L Brade 1, O Holst 1, H Brade 1
PMCID: PMC281192  PMID: 8406846

Abstract

Monoclonal antibodies (MAbs) against lipid A, the endotoxic component of lipopolysaccharide (LPS) of gram-negative bacteria, are presently discussed as therapeutic agents against lethal gram-negative infections; however, their binding specificities are controversial. We have isolated from the LPS of Escherichia coli J-5 the 1,4'-bisphosphorylated beta 1-->6-linked glucosamine disaccharide backbone of its lipid A moiety, which was covalently linked to bovine serum albumin. It was shown by solid-phase enzyme immunoassay that one antibody (MAb A6) bound equally well to the glycoconjugate and synthetic E. coli-type lipid A over a broad range of antigen concentrations whereas two other MAbs (IC3 and S1-15) bound better to the conjugate at low antigen concentrations and better to the lipid A when high concentrations of antigen were used. This proves in a direct way that there exist lipid A MAbs with different specificities which bind to epitopes in the hydrophilic backbone of lipid A and which do not require the presence of fatty acids.

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Selected References

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  1. Appelmelk B. J., Verweij-van Vught A. M., Maaskant J. J., Schouten W. F., De Jonge A. J., Thijs L. G., Maclaren D. M. Production and characterisation of mouse monoclonal antibodies reacting with the lipopolysaccharide core region of gram-negative bacilli. J Med Microbiol. 1988 Jun;26(2):107–114. doi: 10.1099/00222615-26-2-107. [DOI] [PubMed] [Google Scholar]
  2. Baumgartner J. D. Immunotherapy with antibodies to core lipopolysaccharide: a critical appraisal. Infect Dis Clin North Am. 1991 Dec;5(4):915–927. [PubMed] [Google Scholar]
  3. Bogard W. C., Jr, Dunn D. L., Abernethy K., Kilgarriff C., Kung P. C. Isolation and characterization of murine monoclonal antibodies specific for gram-negative bacterial lipopolysaccharide: association of cross-genus reactivity with lipid A specificity. Infect Immun. 1987 Apr;55(4):899–908. doi: 10.1128/iai.55.4.899-908.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brade L., Brandenburg K., Kuhn H. M., Kusumoto S., Macher I., Rietschel E. T., Brade H. The immunogenicity and antigenicity of lipid A are influenced by its physicochemical state and environment. Infect Immun. 1987 Nov;55(11):2636–2644. doi: 10.1128/iai.55.11.2636-2644.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fu Y., Baumann M., Kosma P., Brade L., Brade H. A synthetic glycoconjugate representing the genus-specific epitope of chlamydial lipopolysaccharide exhibits the same specificity as its natural counterpart. Infect Immun. 1992 Apr;60(4):1314–1321. doi: 10.1128/iai.60.4.1314-1321.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Han J., Thompson P., Beutler B. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J Exp Med. 1990 Jul 1;172(1):391–394. doi: 10.1084/jem.172.1.391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holst O., Müller-Loennies S., Lindner B., Brade H. Chemical structure of the lipid A of Escherichia coli J-5. Eur J Biochem. 1993 Jun 15;214(3):695–701. doi: 10.1111/j.1432-1033.1993.tb17970.x. [DOI] [PubMed] [Google Scholar]
  8. Kasai N., Arata S., Mashimo J., Okuda K., Aihara Y., Kotani S., Takada H., Shiba T., Kusumoto S., Imoto M. Synthetic Salmonella-type lipid A antigen with high serological specificity. Infect Immun. 1986 Jan;51(1):43–48. doi: 10.1128/iai.51.1.43-48.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kuhn H. M., Brade L., Appelmelk B. J., Kusumoto S., Rietschel E. T., Brade H. Characterization of the epitope specificity of murine monoclonal antibodies directed against lipid A. Infect Immun. 1992 Jun;60(6):2201–2210. doi: 10.1128/iai.60.6.2201-2210.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROBERTS N. R., LEINER K. Y., WU M. L., FARR A. L. The quantitative histochemistry of brain. I. Chemical methods. J Biol Chem. 1954 Mar;207(1):1–17. [PubMed] [Google Scholar]
  11. Lesslauer W., Tabuchi H., Gentz R., Brockhaus M., Schlaeger E. J., Grau G., Piguet P. F., Pointaire P., Vassalli P., Loetscher H. Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide-induced lethality. Eur J Immunol. 1991 Nov;21(11):2883–2886. doi: 10.1002/eji.1830211134. [DOI] [PubMed] [Google Scholar]
  12. Rietschel E. T., Brade H. Bacterial endotoxins. Sci Am. 1992 Aug;267(2):54–61. doi: 10.1038/scientificamerican0892-54. [DOI] [PubMed] [Google Scholar]
  13. STROMINGER J. L., PARK J. T., THOMPSON R. E. Composition of the cell wall of Staphylococcus aureus: its relation to the mechanism of action of penicillin. J Biol Chem. 1959 Dec;234:3263–3268. [PubMed] [Google Scholar]

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