Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 Oct 1;180(4):1571–1575. doi: 10.1084/jem.180.4.1571

Protection by alpha 1-acid glycoprotein against tumor necrosis factor- induced lethality

PMCID: PMC2191695  PMID: 7931089

Abstract

We here report that alpha 1-acid glycoprotein, a typical acute phase protein, protects mice from lethal shock induced by tumor necrosis factor (TNF) or endotoxin. The protection is observed both in normal and in galactosamine-sensitized mice. Optimal desensitization requires at least 3 mg alpha 1-acid glycoprotein administered 2 h before the lethal challenge. Under these conditions, complete inhibition of all TNF-induced metabolic changes was observed: fall in body temperature, release of liver transaminases, enhanced clotting time, and mortality. The known platelet aggregation-inhibitory activity of alpha 1-acid glycoprotein provides a possible explanation for this protective capacity.

Full Text

The Full Text of this article is available as a PDF (419.2 KB).

Selected References

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

  1. Bories P. N., Feger J., Benbernou N., Rouzeau J. D., Agneray J., Durand G. Prevalence of tri- and tetraantennary glycans of human alpha 1-acid glycoprotein in release of macrophage inhibitor of interleukin-1 activity. Inflammation. 1990 Jun;14(3):315–323. doi: 10.1007/BF00915815. [DOI] [PubMed] [Google Scholar]
  2. Boutten A., Dehoux M., Deschenes M., Rouzeau J. D., Bories P. N., Durand G. Alpha 1-acid glycoprotein potentiates lipopolysaccharide-induced secretion of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha by human monocytes and alveolar and peritoneal macrophages. Eur J Immunol. 1992 Oct;22(10):2687–2695. doi: 10.1002/eji.1830221032. [DOI] [PubMed] [Google Scholar]
  3. Brouckaert P., Libert C., Everaerdt B., Fiers W. Selective species specificity of tumor necrosis factor for toxicity in the mouse. Lymphokine Cytokine Res. 1992 Aug;11(4):193–196. [PubMed] [Google Scholar]
  4. Chan J., Yu D. One-step isolation of alpha 1-acid glycoprotein. Protein Expr Purif. 1991 Feb;2(1):34–36. doi: 10.1016/1046-5928(91)90006-5. [DOI] [PubMed] [Google Scholar]
  5. Costello M., Fiedel B. A., Gewurz H. Inhibition of platelet aggregation by native and desialised alpha-1 acid glycoprotein. Nature. 1979 Oct 25;281(5733):677–678. doi: 10.1038/281677a0. [DOI] [PubMed] [Google Scholar]
  6. Decker K., Keppler D. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol. 1974;(71):77–106. doi: 10.1007/BFb0027661. [DOI] [PubMed] [Google Scholar]
  7. Everaerdt B., Brouckaert P., Fiers W. Recombinant IL-1 receptor antagonist protects against TNF-induced lethality in mice. J Immunol. 1994 May 15;152(10):5041–5049. [PubMed] [Google Scholar]
  8. 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]
  9. Heuertz R. M., Piquette C. A., Webster R. O. Rabbits with elevated serum C-reactive protein exhibit diminished neutrophil infiltration and vascular permeability in C5a-induced alveolitis. Am J Pathol. 1993 Jan;142(1):319–328. [PMC free article] [PubMed] [Google Scholar]
  10. Kopf M., Baumann H., Freer G., Freudenberg M., Lamers M., Kishimoto T., Zinkernagel R., Bluethmann H., Köhler G. Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature. 1994 Mar 24;368(6469):339–342. doi: 10.1038/368339a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Libert C., Van Bladel S., Brouckaert P., Fiers W. The influence of modulating substances on tumor necrosis factor and interleukin-6 levels after injection of murine tumor necrosis factor or lipopolysaccharide in mice. J Immunother (1991) 1991 Aug;10(4):227–235. doi: 10.1097/00002371-199108000-00001. [DOI] [PubMed] [Google Scholar]
  13. Libert C., Van Bladel S., Brouckaert P., Shaw A., Fiers W. Involvement of the liver, but not of IL-6, in IL-1-induced desensitization to the lethal effects of tumor necrosis factor. J Immunol. 1991 Apr 15;146(8):2625–2632. [PubMed] [Google Scholar]
  14. Nagakawa J., Hishinuma I., Hirota K., Miyamoto K., Yamanaka T., Yamatsu I., Katayama K. Protective effects of E3330, a novel quinone derivative, on galactosamine/tumor necrosis factor-alpha-induced hepatitis in mice. Eur J Pharmacol. 1992 Dec 8;229(1):63–67. doi: 10.1016/0014-2999(92)90286-d. [DOI] [PubMed] [Google Scholar]
  15. Piguet P. F., Vesin C., Ryser J. E., Senaldi G., Grau G. E., Tacchini-Cottier F. An effector role for platelets in systemic and local lipopolysaccharide-induced toxicity in mice, mediated by a CD11a- and CD54-dependent interaction with endothelium. Infect Immun. 1993 Oct;61(10):4182–4187. doi: 10.1128/iai.61.10.4182-4187.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reutelingsperger C. P., Hornstra G., Hemker H. C. Isolation and partial purification of a novel anticoagulant from arteries of human umbilical cord. Eur J Biochem. 1985 Sep 16;151(3):625–629. doi: 10.1111/j.1432-1033.1985.tb09150.x. [DOI] [PubMed] [Google Scholar]
  17. Schreiber G., Tsykin A., Aldred A. R., Thomas T., Fung W. P., Dickson P. W., Cole T., Birch H., De Jong F. A., Milland J. The acute phase response in the rodent. Ann N Y Acad Sci. 1989;557:61–86. doi: 10.1111/j.1749-6632.1989.tb24000.x. [DOI] [PubMed] [Google Scholar]
  18. Shainkin-Kestenbaum R., Berlyne G., Zimlichman S., Sorin H. R., Nyska M., Danon A. Acute phase protein, serum amyloid A, inhibits IL-1- and TNF-induced fever and hypothalamic PGE2 in mice. Scand J Immunol. 1991 Aug;34(2):179–183. doi: 10.1111/j.1365-3083.1991.tb01535.x. [DOI] [PubMed] [Google Scholar]
  19. Tilg H., Vannier E., Vachino G., Dinarello C. A., Mier J. W. Antiinflammatory properties of hepatic acute phase proteins: preferential induction of interleukin 1 (IL-1) receptor antagonist over IL-1 beta synthesis by human peripheral blood mononuclear cells. J Exp Med. 1993 Nov 1;178(5):1629–1636. doi: 10.1084/jem.178.5.1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Tracey K. J., Cerami A. Tumor necrosis factor, other cytokines and disease. Annu Rev Cell Biol. 1993;9:317–343. doi: 10.1146/annurev.cb.09.110193.001533. [DOI] [PubMed] [Google Scholar]
  21. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452. doi: 10.1146/annurev.iy.10.040192.002211. [DOI] [PubMed] [Google Scholar]
  22. Wallach D., Holtmann H., Engelmann H., Nophar Y. Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1. J Immunol. 1988 May 1;140(9):2994–2999. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES