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. 1994 Aug;62(8):3564–3567. doi: 10.1128/iai.62.8.3564-3567.1994

Recombinant human bactericidal/permeability-increasing protein (rBPI23) is a universal lipopolysaccharide-binding ligand.

B J Appelmelk 1, Y Q An 1, B G Thijs 1, D M MacLaren 1, J de Graaff 1
PMCID: PMC302994  PMID: 8039930

Abstract

A recombinant 23-kDa protein (rBPI23) derived from human bactericidal/permeability-increasing protein (BPI) possesses potent endotoxin-neutralizing abilities in vitro and in vivo. Binding of rBPI23 to those endotoxins (lipopolysaccharides [LPSs]) encountered clinically would be a prerequisite for efficacy in decreasing mortality among patients suffering from gram-negative sepsis and shock, a disease state in which an etiological role for LPS has been implicated. rBPI23 binds well to lipid A (n = 7), to rough-mutant O-chain-deficient LPS (n = 18, Re to Ra chemotypes), to lipid A-core covalently linked to the O chain, to LPSs from clinically relevant serotypes (n = 100), and to bacterial cells (n = 88) of Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, the species most often implicated in clinical gram-negative sepsis and shock. Significant binding of rBPI23 to these antigens took place at rBPI23 concentrations of 1 to 500 ng/ml (median, 16 to 32 ng/ml). Binding did not involve 3-deoxy-D-manno-octulosonate of the inner core. Determining the exact epitope recognized by rBPI23 would require further studies with synthetic lipid A substructures. The demonstrated ability of rBPI23 to universally bind LPS provides a sound basis for further testing of its endotoxin-neutralizing abilities, including clinical trials.

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Selected References

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  1. Brade L., Kosma P., Appelmelk B. J., Paulsen H., Brade H. Use of synthetic antigens to determine the epitope specificities of monoclonal antibodies against the 3-deoxy-D-manno-octulosonate region of bacterial lipopolysaccharide. Infect Immun. 1987 Feb;55(2):462–466. doi: 10.1128/iai.55.2.462-466.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cryz S. J., Jr, Fürer E., Sadoff J. C., Germanier R. A polyvalent Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. Antibiot Chemother (1971) 1987;39:249–255. doi: 10.1159/000414350. [DOI] [PubMed] [Google Scholar]
  3. Di Padova F. E., Brade H., Barclay G. R., Poxton I. R., Liehl E., Schuetze E., Kocher H. P., Ramsay G., Schreier M. H., McClelland D. B. A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides. Infect Immun. 1993 Sep;61(9):3863–3872. doi: 10.1128/iai.61.9.3863-3872.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Elsbach P., Weiss J. Bactericidal/permeability increasing protein and host defense against gram-negative bacteria and endotoxin. Curr Opin Immunol. 1993 Feb;5(1):103–107. doi: 10.1016/0952-7915(93)90088-a. [DOI] [PubMed] [Google Scholar]
  5. Fujita S., Matsubara F. Latex agglutination text for O serogrouping of Klebsiella species. Microbiol Immunol. 1984;28(6):731–734. doi: 10.1111/j.1348-0421.1984.tb00728.x. [DOI] [PubMed] [Google Scholar]
  6. Gazzano-Santoro H., Parent J. B., Grinna L., Horwitz A., Parsons T., Theofan G., Elsbach P., Weiss J., Conlon P. J. High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide. Infect Immun. 1992 Nov;60(11):4754–4761. doi: 10.1128/iai.60.11.4754-4761.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kohn F. R., Ammons W. S., Horwitz A., Grinna L., Theofan G., Weickmann J., Kung A. H. Protective effect of a recombinant amino-terminal fragment of bactericidal/permeability-increasing protein in experimental endotoxemia. J Infect Dis. 1993 Nov;168(5):1307–1310. doi: 10.1093/infdis/168.5.1307. [DOI] [PubMed] [Google Scholar]
  8. Komuro T., Yomota C., Isaka H. Sodium deoxycholate-polyacrylamide gel electrophoresis of lipopolysaccharides at low temperature. Chem Pharm Bull (Tokyo) 1988 Mar;36(3):1218–1222. doi: 10.1248/cpb.36.1218. [DOI] [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. Marra M. N., Wilde C. G., Collins M. S., Snable J. L., Thornton M. B., Scott R. W. The role of bactericidal/permeability-increasing protein as a natural inhibitor of bacterial endotoxin. J Immunol. 1992 Jan 15;148(2):532–537. [PubMed] [Google Scholar]
  11. McCabe W. R., Kaijser B., Olling S., Uwaydah M., Hanson L. A. Escherichia coli in bacteremia: K and O antigens and serum sensitivity of strains from adults and neonates. J Infect Dis. 1978 Jul;138(1):33–41. doi: 10.1093/infdis/138.1.33. [DOI] [PubMed] [Google Scholar]
  12. Ooi C. E., Weiss J., Doerfler M. E., Elsbach P. Endotoxin-neutralizing properties of the 25 kD N-terminal fragment and a newly isolated 30 kD C-terminal fragment of the 55-60 kD bactericidal/permeability-increasing protein of human neutrophils. J Exp Med. 1991 Sep 1;174(3):649–655. doi: 10.1084/jem.174.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Tobias P. S., Soldau K., Ulevitch R. J. Identification of a lipid A binding site in the acute phase reactant lipopolysaccharide binding protein. J Biol Chem. 1989 Jun 25;264(18):10867–10871. [PubMed] [Google Scholar]
  14. van der Meer N. M., Appelmelk B. J., Verweij-van Vught A. M., Nimmich W., Kosma P., Thijs L. G., de Graaff J., MacLaren D. M. Binding studies of a monoclonal antibody specific for 3-deoxy-D-manno-octulosonic acid with a panel of Klebsiella pneumoniae lipopolysaccharides representing all of the O serotypes. Infect Immun. 1994 Mar;62(3):1052–1057. doi: 10.1128/iai.62.3.1052-1057.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]

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