Abstract
The apoptotic cell death induced in D-galactosamine-sensitized mice by administration of lipopolysaccharide was characterized. Administration of lipopolysaccharide caused apoptotic cell death in livers of D-galactosamine-sensitized mice. Apoptotic cells were also detected in the kidney, thymus, spleen, and lymph node. Severe hepatic apoptosis in D-galactosamine-sensitized mice was reproduced by transfer of the sera from mice injected with D-galactosamine and lipopolysaccharide. The hepatocyte apoptosis induced by lipopolysaccharide was completely prevented by an anti-tumor necrosis factor alpha antibody but not by an anti-gamma interferon antibody. Administration of recombinant tumor necrosis factor into D-galactosamine-sensitized mice also caused hepatocyte apoptosis. Lipopolysaccharide-induced hepatocyte apoptosis in D-galactosamine-sensitized mice did not seem to be mediated by Fas antigen. It was suggested that lipopolysaccharide- induced hepatic injury and failure in D-galactosamine-sensitized mice was due to the apoptotic cell death of hepatocytes caused by tumor necrosis factor alpha released in the circulation.
Full Text
The Full Text of this article is available as a PDF (986.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adachi M., Watanabe-Fukunaga R., Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756–1760. doi: 10.1073/pnas.90.5.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cohen J. J. Programmed cell death in the immune system. Adv Immunol. 1991;50:55–85. doi: 10.1016/s0065-2776(08)60822-6. [DOI] [PubMed] [Google Scholar]
- Dealtry G. B., Naylor M. S., Fiers W., Balkwill F. R. DNA fragmentation and cytotoxicity caused by tumor necrosis factor is enhanced by interferon-gamma. Eur J Immunol. 1987 May;17(5):689–693. doi: 10.1002/eji.1830170517. [DOI] [PubMed] [Google Scholar]
- Doherty G. M., Lange J. R., Langstein H. N., Alexander H. R., Buresh C. M., Norton J. A. Evidence for IFN-gamma as a mediator of the lethality of endotoxin and tumor necrosis factor-alpha. J Immunol. 1992 Sep 1;149(5):1666–1670. [PubMed] [Google Scholar]
- Facchinetti A., Tessarollo L., Mazzocchi M., Kingston R., Collavo D., Biasi G. An improved method for the detection of DNA fragmentation. J Immunol Methods. 1991 Jan 24;136(1):125–131. doi: 10.1016/0022-1759(91)90258-h. [DOI] [PubMed] [Google Scholar]
- 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]
- Gavrieli Y., Sherman Y., Ben-Sasson S. A. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol. 1992 Nov;119(3):493–501. doi: 10.1083/jcb.119.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golstein P., Ojcius D. M., Young J. D. Cell death mechanisms and the immune system. Immunol Rev. 1991 Jun;121:29–65. doi: 10.1111/j.1600-065x.1991.tb00822.x. [DOI] [PubMed] [Google Scholar]
- Hernández-Caselles T., Stutman O. Immune functions of tumor necrosis factor. I. Tumor necrosis factor induces apoptosis of mouse thymocytes and can also stimulate or inhibit IL-6-induced proliferation depending on the concentration of mitogenic costimulation. J Immunol. 1993 Oct 15;151(8):3999–4012. [PubMed] [Google Scholar]
- Kerr J. F., Wyllie A. H., Currie A. R. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972 Aug;26(4):239–257. doi: 10.1038/bjc.1972.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Leist M., Gantner F., Bohlinger I., Germann P. G., Tiegs G., Wendel A. Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-alpha requires transcriptional arrest. J Immunol. 1994 Aug 15;153(4):1778–1788. [PubMed] [Google Scholar]
- Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature. 1993 Aug 26;364(6440):806–809. doi: 10.1038/364806a0. [DOI] [PubMed] [Google Scholar]
- Tiegs G., Wolter M., Wendel A. Tumor necrosis factor is a terminal mediator in galactosamine/endotoxin-induced hepatitis in mice. Biochem Pharmacol. 1989 Feb 15;38(4):627–631. doi: 10.1016/0006-2952(89)90208-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Wang S. D., Huang K. J., Lin Y. S., Lei H. Y. Sepsis-induced apoptosis of the thymocytes in mice. J Immunol. 1994 May 15;152(10):5014–5021. [PubMed] [Google Scholar]
- Wyllie A. H., Kerr J. F., Currie A. R. Cell death: the significance of apoptosis. Int Rev Cytol. 1980;68:251–306. doi: 10.1016/s0074-7696(08)62312-8. [DOI] [PubMed] [Google Scholar]
- Zhang X. M., Morikawa A., Takahashi K., Jiang G. Z., Kato Y., Sugiyama T., Kawai M., Fukada M., Yokochi T. Localization of apoptosis (programmed cell death) in mice by administration of lipopolysaccharide. Microbiol Immunol. 1994;38(8):669–671. doi: 10.1111/j.1348-0421.1994.tb01838.x. [DOI] [PubMed] [Google Scholar]
- Zhang Y. H., Takahashi K., Jiang G. Z., Kawai M., Fukada M., Yokochi T. In vivo induction of apoptosis (programmed cell death) in mouse thymus by administration of lipopolysaccharide. Infect Immun. 1993 Dec;61(12):5044–5048. doi: 10.1128/iai.61.12.5044-5048.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]