Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Nov 1;90(21):9935–9938. doi: 10.1073/pnas.90.21.9935

Lipopolysaccharide-binding protein as a major plasma protein responsible for endotoxemic shock.

P Gallay 1, D Heumann 1, D Le Roy 1, C Barras 1, M P Glauser 1
PMCID: PMC47687  PMID: 7694297

Abstract

Because lipopolysaccharide (LPS)-binding protein (LBP) sensitizes monocytes to LPS in vitro, it has been suggested that LBP initiates host defenses against Gram-negative bacteria. The role of LBP in vivo, and particularly in endotoxemic shock, is unknown, however. Therefore an IgG against murine LBP was prepared. It was found to neutralize binding of LPS and subsequent activation of murine macrophages in vitro. This anti-LBP protected mice against the lethal effect of LPS when given at the same time as LPS challenge, but it failed to protect mice when delayed 15 min after LPS challenge. The same preparation was also effective after challenge with lipid A but not after challenge with Staphylococcus aureus enterotoxin. The protection was correlated with a strong decrease of circulating tumor necrosis factor. These data demonstrate that in vivo LBP is a major mediator of the lethal effects of endotoxemia.

Full text

PDF
9935

Images in this article

9936Fig. 1
on p.9936

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baumgartner J. D., Heumann D., Gerain J., Weinbreck P., Grau G. E., Glauser M. P. Association between protective efficacy of anti-lipopolysaccharide (LPS) antibodies and suppression of LPS-induced tumor necrosis factor alpha and interleukin 6. Comparison of O side chain-specific antibodies with core LPS antibodies. J Exp Med. 1990 Mar 1;171(3):889–896. doi: 10.1084/jem.171.3.889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  3. Corradin S. B., Mauël J., Gallay P., Heumann D., Ulevitch R. J., Tobias P. S. Enhancement of murine macrophage binding of and response to bacterial lipopolysaccharide (LPS) by LPS-binding protein. J Leukoc Biol. 1992 Oct;52(4):363–368. doi: 10.1002/jlb.52.4.363. [DOI] [PubMed] [Google Scholar]
  4. Freudenberg M. A., Galanos C. Tumor necrosis factor alpha mediates lethal activity of killed gram-negative and gram-positive bacteria in D-galactosamine-treated mice. Infect Immun. 1991 Jun;59(6):2110–2115. doi: 10.1128/iai.59.6.2110-2115.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Galanos C., Freudenberg M. A., Reutter W. Galactosamine-induced sensitization to the lethal effects of endotoxin. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5939–5943. doi: 10.1073/pnas.76.11.5939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gallay P., Carrel S., Glauser M. P., Barras C., Ulevitch R. J., Tobias P. S., Baumgartner J. D., Heumann D. Purification and characterization of murine lipopolysaccharide-binding protein. Infect Immun. 1993 Feb;61(2):378–383. doi: 10.1128/iai.61.2.378-383.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Glauser M. P., Zanetti G., Baumgartner J. D., Cohen J. Septic shock: pathogenesis. Lancet. 1991 Sep 21;338(8769):732–736. doi: 10.1016/0140-6736(91)91452-z. [DOI] [PubMed] [Google Scholar]
  8. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  9. Heumann D., Baumgartner J. D., Jacot-Guillarmod H., Glauser M. P. Antibodies to core lipopolysaccharide determinants: absence of cross-reactivity with heterologous lipopolysaccharides. J Infect Dis. 1991 Apr;163(4):762–768. doi: 10.1093/infdis/163.4.762. [DOI] [PubMed] [Google Scholar]
  10. Heumann D., Gallay P., Barras C., Zaech P., Ulevitch R. J., Tobias P. S., Glauser M. P., Baumgartner J. D. Control of lipopolysaccharide (LPS) binding and LPS-induced tumor necrosis factor secretion in human peripheral blood monocytes. J Immunol. 1992 Jun 1;148(11):3505–3512. [PubMed] [Google Scholar]
  11. 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]
  12. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lei M. G., Chen T. Y., Morrison D. C. Lipopolysaccharide/lipid A receptors on lymphocytes and macrophages. Int Rev Immunol. 1990;6(4):223–235. doi: 10.3109/08830189009056633. [DOI] [PubMed] [Google Scholar]
  14. Raetz C. R., Ulevitch R. J., Wright S. D., Sibley C. H., Ding A., Nathan C. F. Gram-negative endotoxin: an extraordinary lipid with profound effects on eukaryotic signal transduction. FASEB J. 1991 Sep;5(12):2652–2660. doi: 10.1096/fasebj.5.12.1916089. [DOI] [PubMed] [Google Scholar]
  15. Schumann R. R., Leong S. R., Flaggs G. W., Gray P. W., Wright S. D., Mathison J. C., Tobias P. S., Ulevitch R. J. Structure and function of lipopolysaccharide binding protein. Science. 1990 Sep 21;249(4975):1429–1431. doi: 10.1126/science.2402637. [DOI] [PubMed] [Google Scholar]
  16. Schweinle J. E., Nishiyasu M., Ding T. Q., Sastry K., Gillies S. D., Ezekowitz R. A. Truncated forms of mannose-binding protein multimerize and bind to mannose-rich Salmonella montevideo but fail to activate complement in vitro. J Biol Chem. 1993 Jan 5;268(1):364–370. [PubMed] [Google Scholar]
  17. Tobias P. S., Soldau K., Ulevitch R. J. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J Exp Med. 1986 Sep 1;164(3):777–793. doi: 10.1084/jem.164.3.777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tracey K. J., Lowry S. F. The role of cytokine mediators in septic shock. Adv Surg. 1990;23:21–56. [PubMed] [Google Scholar]
  20. Wright S. D., Ramos R. A., Patel M., Miller D. S. Septin: a factor in plasma that opsonizes lipopolysaccharide-bearing particles for recognition by CD14 on phagocytes. J Exp Med. 1992 Sep 1;176(3):719–727. doi: 10.1084/jem.176.3.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Wright S. D., Ramos R. A., Tobias P. S., Ulevitch R. J., Mathison J. C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science. 1990 Sep 21;249(4975):1431–1433. doi: 10.1126/science.1698311. [DOI] [PubMed] [Google Scholar]
  22. Zanetti G., Heumann D., Gérain J., Kohler J., Abbet P., Barras C., Lucas R., Glauser M. P., Baumgartner J. D. Cytokine production after intravenous or peritoneal gram-negative bacterial challenge in mice. Comparative protective efficacy of antibodies to tumor necrosis factor-alpha and to lipopolysaccharide. J Immunol. 1992 Mar 15;148(6):1890–1897. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES