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. 1995 Mar;63(3):1122–1126. doi: 10.1128/iai.63.3.1122-1126.1995

Lipopolysaccharide-induced apoptosis in swine lymphocytes in vivo.

M Norimatsu 1, T Ono 1, A Aoki 1, K Ohishi 1, T Takahashi 1, G Watanabe 1, K Taya 1, S Sasamoto 1, Y Tamura 1
PMCID: PMC173120  PMID: 7868236

Abstract

The in vivo effects of bacterial lipopolysaccharide (LPS) on the immune systems of piglets were investigated. Intravenous injection of 0.5 mg of LPS per kilogram of body weight induced apoptosis, which was characterized by nuclear chromatin condensation and fragmentation and a ladder formation of nucleosomal DNA in lymphocytes both in the cortex of the thymus and in the germinal centers and paracortical areas of mesenteric lymph nodes at 24 h postinjection. The levels of endotoxin, tumor necrosis factor alpha, and cortisol in serum increased, generally according to the dose of LPS. These findings suggest that LPS can induce in vivo apoptosis of lymphocytes in piglets and support the notion that cytokine and endocrine responses may play an important role in LPS-induced apoptosis in the immune system.

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Selected References

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  1. Ashwell J. D., Berger N. A., Cidlowski J. A., Lane D. P., Korsmeyer S. J. Coming to terms with death: apoptosis in cancer and immune development. Immunol Today. 1994 Apr;15(4):147–151. doi: 10.1016/0167-5699(94)90309-3. [DOI] [PubMed] [Google Scholar]
  2. Barber A. E., Coyle S. M., Marano M. A., Fischer E., Calvano S. E., Fong Y., Moldawer L. L., Lowry S. F. Glucocorticoid therapy alters hormonal and cytokine responses to endotoxin in man. J Immunol. 1993 Mar 1;150(5):1999–2006. [PubMed] [Google Scholar]
  3. Baroni C. D., De Franceschi G. S., Uccini S., Adorini L., Cnen G. D., Ruco L. Biological effects of Escherichia coli lipopolysaccharide (LPS) in vivo. I. Selection in the mouse thymus of killer and helper cells. Immunology. 1976 Aug;31(2):217–224. [PMC free article] [PubMed] [Google Scholar]
  4. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  5. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  6. Brown-Borg H. M., Klemcke H. G., Blecha F. Lymphocyte proliferative responses in neonatal pigs with high or low plasma cortisol concentration after stress induced by restraint. Am J Vet Res. 1993 Dec;54(12):2015–2020. [PubMed] [Google Scholar]
  7. 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]
  8. Gonzalez J. C., Johnson D. C., Morrison D. C., Freudenberg M. A., Galanos C., Silverstein R. Endogenous and exogenous glucocorticoids have different roles in modulating endotoxin lethality in D-galactosamine-sensitized mice. Infect Immun. 1993 Mar;61(3):970–974. doi: 10.1128/iai.61.3.970-974.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hansen M. B., Nielsen S. E., Berg K. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J Immunol Methods. 1989 May 12;119(2):203–210. doi: 10.1016/0022-1759(89)90397-9. [DOI] [PubMed] [Google Scholar]
  11. Landy M., Baker P. J. Cytodynamics of the distinctive immune response produced in regional lymph nodes by Salmonella somatic polysaccharide. J Immunol. 1966 Nov;97(5):670–679. [PubMed] [Google Scholar]
  12. Lee S. W., Tsou A. P., Chan H., Thomas J., Petrie K., Eugui E. M., Allison A. C. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1204–1208. doi: 10.1073/pnas.85.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lew W., Oppenheim J. J., Matsushima K. Analysis of the suppression of IL-1 alpha and IL-1 beta production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J Immunol. 1988 Mar 15;140(6):1895–1902. [PubMed] [Google Scholar]
  14. Michalek S. M., Moore R. N., McGhee J. R., Rosenstreich D. L., Mergenhagen S. E. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxim. J Infect Dis. 1980 Jan;141(1):55–63. doi: 10.1093/infdis/141.1.55. [DOI] [PubMed] [Google Scholar]
  15. Mogil R. J., Shi Y., Bissonnette R. P., Bromley P., Yamaguchi I., Green D. R. Role of DNA fragmentation in T cell activation-induced apoptosis in vitro and in vivo. J Immunol. 1994 Feb 15;152(4):1674–1683. [PubMed] [Google Scholar]
  16. Morrison D. C., Ryan J. L. Bacterial endotoxins and host immune responses. Adv Immunol. 1979;28:293–450. doi: 10.1016/s0065-2776(08)60802-0. [DOI] [PubMed] [Google Scholar]
  17. Morrison D. C., Ryan J. L. Endotoxins and disease mechanisms. Annu Rev Med. 1987;38:417–432. doi: 10.1146/annurev.me.38.020187.002221. [DOI] [PubMed] [Google Scholar]
  18. Mukaida N., Zachariae C. C., Gusella G. L., Matsushima K. Dexamethasone inhibits the induction of monocyte chemotactic-activating factor production by IL-1 or tumor necrosis factor. J Immunol. 1991 Feb 15;146(4):1212–1215. [PubMed] [Google Scholar]
  19. Munck A., Guyre P. M., Holbrook N. J. Physiological functions of glucocorticoids in stress and their relation to pharmacological actions. Endocr Rev. 1984 Winter;5(1):25–44. doi: 10.1210/edrv-5-1-25. [DOI] [PubMed] [Google Scholar]
  20. Perlstein R. S., Whitnall M. H., Abrams J. S., Mougey E. H., Neta R. Synergistic roles of interleukin-6, interleukin-1, and tumor necrosis factor in the adrenocorticotropin response to bacterial lipopolysaccharide in vivo. Endocrinology. 1993 Mar;132(3):946–952. doi: 10.1210/endo.132.3.8382602. [DOI] [PubMed] [Google Scholar]
  21. Remick D. G., Strieter R. M., Lynch J. P., 3rd, Nguyen D., Eskandari M., Kunkel S. L. In vivo dynamics of murine tumor necrosis factor-alpha gene expression. Kinetics of dexamethasone-induced suppression. Lab Invest. 1989 Jun;60(6):766–771. [PubMed] [Google Scholar]
  22. Rivier C., Chizzonite R., Vale W. In the mouse, the activation of the hypothalamic-pituitary-adrenal axis by a lipopolysaccharide (endotoxin) is mediated through interleukin-1. Endocrinology. 1989 Dec;125(6):2800–2805. doi: 10.1210/endo-125-6-2800. [DOI] [PubMed] [Google Scholar]
  23. Roeder D. J., Lei M. G., Morrison D. C. Endotoxic-lipopolysaccharide-specific binding proteins on lymphoid cells of various animal species: association with endotoxin susceptibility. Infect Immun. 1989 Apr;57(4):1054–1058. doi: 10.1128/iai.57.4.1054-1058.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stine D. L., Huether M. J., Moxley R. A., Srikumaran S. Actinobacillus pleuropneumoniae-induced thymic lesions in mice and pigs. Infect Immun. 1991 Sep;59(9):2885–2891. doi: 10.1128/iai.59.9.2885-2891.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waage A., Bakke O. Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology. 1988 Feb;63(2):299–302. [PMC free article] [PubMed] [Google Scholar]
  26. Wyllie A. H. Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature. 1980 Apr 10;284(5756):555–556. doi: 10.1038/284555a0. [DOI] [PubMed] [Google Scholar]
  27. Yokochi T., Nakashima I., Kato N. Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. VIII. Its effect on the size and the number of cells of regional lymph node and other lymphoid organs. Microbiol Immunol. 1980;24(2):141–154. doi: 10.1111/j.1348-0421.1980.tb00572.x. [DOI] [PubMed] [Google Scholar]
  28. Yokochi T., Nakashima I., Kato N., Asai J., Iijima S. Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IX. Its effect on the histology of the regional lymph node and other lymphoid organs. Microbiol Immunol. 1980;24(10):933–944. doi: 10.1111/j.1348-0421.1980.tb02899.x. [DOI] [PubMed] [Google Scholar]
  29. Zacharchuk C. M., Merćep M., Chakraborti P. K., Simons S. S., Jr, Ashwell J. D. Programmed T lymphocyte death. Cell activation- and steroid-induced pathways are mutually antagonistic. J Immunol. 1990 Dec 15;145(12):4037–4045. [PubMed] [Google Scholar]
  30. 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]
  31. Zuckerman S. H., Bendele A. M. Regulation of serum tumor necrosis factor in glucocorticoid-sensitive and -resistant rodent endotoxin shock models. Infect Immun. 1989 Oct;57(10):3009–3013. doi: 10.1128/iai.57.10.3009-3013.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zuckerman S. H., Qureshi N. In vivo inhibition of lipopolysaccharide-induced lethality and tumor necrosis factor synthesis by Rhodobacter sphaeroides diphosphoryl lipid A is dependent on corticosterone induction. Infect Immun. 1992 Jul;60(7):2581–2587. doi: 10.1128/iai.60.7.2581-2587.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zuckerman S. H., Shellhaas J., Butler L. D. Differential regulation of lipopolysaccharide-induced interleukin 1 and tumor necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol. 1989 Feb;19(2):301–305. doi: 10.1002/eji.1830190213. [DOI] [PubMed] [Google Scholar]

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