The Radioprotective Effect of Bacterial Endotoxin

  • Ulrich H. Behling


The exposure of a mammal to a single whole-body dose of rapidly delivered ionizing radiation of approximately 100 R or more results in the development of a complex set of clinical signs and symptoms that are collectively termed the acute radiation syndrome (Cronkite, 1964; Wald et al., 1962). The time of onset, nature, and severity of this syndrome are a function of the total exposure dose, quality of radiation, and many variables related to the irradiated host. In most of the experimental work described here, X- or γ-radiation was delivered uniformly to the entire body in a single exposure lasting on the order of minutes. The dosage of radiation in these experiments fell within the range of threshold lethal, for this represents the minimum amount of radiation causing death within 30 days of exposure. Peak incidence of mortality for the midlethal dose (LD50/30) generally occurs between 10 and 14 days following irradiation. Whole-body irradiation in this dose range produces a complex series of physiological disturbances and morphological changes that are the cumulative results of radiation-induced damage or death of individual cells.


Bacterial Endotoxin Irradiate Mouse Radioprotective Effect Hemopoietic Tissue Radioprotective Property 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ainsworth, E. J., and Chase, H. B., 1959, Effect of microbial antigens on irradiation mortality in mice, Proc. Soc. Exp. Biol. Med. 102:483.PubMedGoogle Scholar
  2. Armerding, D., and Katz, D. H., 1974, Activation of T and B lymphocytes in vitro: Regulatory influence of bacterial lipopolysaccharide (LPS) on specific T helper cell function,J. Exp. Med. 139:24.PubMedCrossRefGoogle Scholar
  3. Arrendondo, M. T., and Kampschmidt, R. F., 1963, Effect of endotoxins on phagocytic activity of the reticuloendothelial system of the rat,J. Exp. Biol. Med. 112:78.Google Scholar
  4. Athens, J. W., Raab, S. O., Haab, O. P., Mauer, A. M., and Ashenbrucker, H., 1961a, Leukokinetic studies. III. The distribution of granulocytes in the blood of normal subjects,J. Clin. Invest. 40:159.PubMedCrossRefGoogle Scholar
  5. Athens, J. W., Haab, O. P., Raab, S. O., Mauer, A. M., Ashenbrucker, H., Cartwright, G. E., and Wintrobe, M. M., 1961b, Leukokinetic studies. IV. The total blood, circulating and marginal granulocyte pools and the granulocyte turnover rate in normal subjects,J. Clin. Invest. 40:989.PubMedCrossRefGoogle Scholar
  6. Behling, U. H., 1982, Bacterial endotoxins as modulators of specific and nonspecific immunity, in: Regulatory Implications of Oscillatory Dynamics in the Immune System (C. De Lisi and A. Hiernaux, eds.), CRC Press, Boca Raton, in press.Google Scholar
  7. Behling, U. H., and Nowotny, A., 1978, Long-term adjuvant effect of bacterial endotoxin in prevention and restoration of radiation-caused immunosuppression, Proc. Soc. Exp. Biol. Med. 157:348.PubMedGoogle Scholar
  8. Behling, U. H., and Nowotny, A., 1980, Cyclic changes of positive and negative effects of single endotoxin injections, in: Bacterial Endotoxins and Host Response (M. K. Agarwal, ed.), pp. 11–26, Elsevier/North-Holland, Amsterdam.Google Scholar
  9. Benacerraf, B., 1960, Influence of irradiation on resistance to infection, Bacteriol. Rev. 24:35.PubMedGoogle Scholar
  10. Benjamin, E., and Sluka, E., 1908, Antikorperbildung Nach Experimenteller Schadigung des Haematopoetischen Systems durch Roentgenstrahlen, Wien. Klin. Wochenschr. 21:311.Google Scholar
  11. Bond, V. P., 1957, The role of infection in illness following exposure to acute total-body irradiation, Bull. N.Y. Acad. Med. 33:369.Google Scholar
  12. Boyse, E. A., Meyazawa, M., Aoki, T., and Old, L. T., 1968, Ly-A and Ly-B: Two systems of lymphocyte isoantigens in the mouse, Proc. R. Soc. London Ser. B 170:175.CrossRefGoogle Scholar
  13. Carswell, E. A., Old, L. J., Kassel, R. L., Green, S., Fiore, N., and Williamson, B., 1975, An endotoxin-induced serum factor that causes necrosis of tumors, Proc. Xatl. Acad. Sci. USA 72:3666.CrossRefGoogle Scholar
  14. Charlton, D. E., and Cormack, D. V., 1962, Energy dissipation in finite cavities, Radiat. Res. 17:34.PubMedCrossRefGoogle Scholar
  15. Chen, C. H., Johnson, A. G., Kasai, N., Key, B. A., Levin, J. and Nowotny, A., 1973, Heterogeneity and biological activity of endotoxic glycolipid from Salmonella minnesota R595,J. Infect. Dis. 128(Suppl.):43.PubMedCrossRefGoogle Scholar
  16. Cole, L. J., and Ellis, M. E., 1953, Age, strain and species factors in post-irradiation protection by spleen homogenates, Am. J. Physiol. 173:487.PubMedGoogle Scholar
  17. Cronkite, E. P., 1964, in: Atomic Medicine, pp. 170–188, Williams & Wilkins, Baltimore.Google Scholar
  18. Cronkite, E. P., 1964, in: Atomic Medicine, pp. 192–196, Williams & Wilkins, Baltimore.Google Scholar
  19. Cronkite, E. P., 1973, Radiosensitivity of lymphocytes, Strahlenschutz Forsch. Prax 13:13.PubMedGoogle Scholar
  20. Cronkite, E. P., and Bond, V. P., 1956, Effect of radiation on mammals, Annu. Rev. Physiol. 18:483.PubMedCrossRefGoogle Scholar
  21. Doe, W. F., and Henson, P. M., 1978, Macrophage stimulation by bacterial lipopolysaccharides. I. Cytolytic effect on tumor target cells,J. Exp. Med. 148:544.PubMedCrossRefGoogle Scholar
  22. Dubos, R. J., and Schaedler, R. W., 1956, Reversible changes in the susceptibility of mice to bacterial infections,J. Exp. Med. 104:53.PubMedCrossRefGoogle Scholar
  23. Ernstrom, U., 1972, Effect of irradiation on the release of lymphocytes from the thymus, Acta Radiol. 11:257.CrossRefGoogle Scholar
  24. Farrar, J. J., Simon, P. L., Koopman, W. J., and Fuller-Bonar, J., 1978, Biochemical relationship of thymocyte mitogenic factor and factors enhancing humoral and cell-mediated immune responses,J. Immunol. 121:1358.Google Scholar
  25. Cell, P. G. H., and Benacerraf, B., 1961, Delayed hypersensitivity to simple protein antigens, Adv. Immunol. 1:319.CrossRefGoogle Scholar
  26. Gery, I., and Waksman, B. H., 1972, Potentiation of the T-lymphocyte response. II. The cellular source of potentiating mediator(s),J. Exp. Med. 136:143.PubMedCrossRefGoogle Scholar
  27. Gidali, J., Feher, I., and Varteresz, V., 1969, The effect of endotoxin on the growth and differentiation of haemopoietic stem cells, Atomkernenergie 14:235.Google Scholar
  28. Goodwin, J. S., and Webb, D. R., 1980, Regulation of the immune response by prostaglandins, Clin. Immunol. Immunopathol. 15:106.PubMedCrossRefGoogle Scholar
  29. Gurney, C. W., 1963, Effect of radiation on the mouse stem cell compartment in vivo, Perspect. Biol. Med. 6:233.PubMedGoogle Scholar
  30. Hoffmann, M. K., Koenig, S., Mittler, R. S., Oettgen, H. F., Ralph, P., Galanos, C., and Hämmerling, U., 1979a, Macrophage factor controlling differentiation of B-cells,J. Immunol. 122:497.PubMedGoogle Scholar
  31. Hoffmann, M. K., Galanos, C., Koenig, S., and Oettgen, H. F., 1979b, B-Cell activation by lipopolysaccharide: Distinct pathways for induction of mitosis and antibody production,J. Exp. Med. 146:1640.CrossRefGoogle Scholar
  32. Hulse, E. Y., 1959, Eymphocyte depletion of the blood and bone marrow of the irradiated rat: A quantitative study, Br. J. Haematol. 5:278.PubMedCrossRefGoogle Scholar
  33. Kennedy, J. C., Fill, J. E., and Siminovitch, E., 1965, Radiosensitivity of the immune response to sheep red cells in the mouse as measured by the haemolytic plaque method,J. Immunol. 94:715.PubMedGoogle Scholar
  34. Kinosita, R., Nowotny, A., and Shikato, T., 1963, Conference on bone marrow transplantation and chemical protection in large animals and man, Blood 21:779.Google Scholar
  35. Kiser, J. S., Lindh, H., and diMello, G. C., 1956, The effect of various substances on resistance to experimental infections, Ann. N.Y. Acad. Sci. 66:312.CrossRefGoogle Scholar
  36. Kisielov, P., Hirst, J., Shiku, H., Beverly, P. C. E., Hoffmann, M. K., Boyse, E. A., and Oettgen, H. F., 1975, Ly antigens as markers for functionally distinct subpopulations of thymus derived lymphocytes of the mouse, Nature (London) 253:219.CrossRefGoogle Scholar
  37. Koopman, W. J., Farrar, J. J., and Fuller-Bonar, J., 1978, Evidence for the identification of lymphocyte activating factor as the adherent cell-derived mediator responsible for enhanced antibody synthesis by nude mouse spleen cells, Cell. Immunol. 35:92.PubMedCrossRefGoogle Scholar
  38. Landy, M., 1956, Increased resistance to infection developed rapidly after administration of bacterial lipopolysaccharides, Fed. Proc. 15:598.Google Scholar
  39. Landy, M., and Pillemer, L., 1956, Increased resistance to infection and accompanying alteration in properdin levels following administration of bacterial lipopolysaccharides,J. Exp. Med. 104:383.PubMedCrossRefGoogle Scholar
  40. Landy, M., and Weidans, W. P., 1964, in: Bacterial Endotoxins (M. Landy and W. Braun, eds.), Rutgers University Press, New Brunswick, N.J.Google Scholar
  41. Lawrence, H. S. (ed.), 1959, Cellular and Humoral Aspects of the Hypersensitive states, Harper & Row (Hoeber), New York.Google Scholar
  42. Lentsch, J. W., and Finston, R. A., 1967, Increased x-ray dose adjacent to plane bone interfaces as measured by polyethylene, Phys. Med. Biol. 12(4):543.PubMedCrossRefGoogle Scholar
  43. Linman, J. W., and Bethall, F. H., 1957, The effect of irradiation on the plasma erythropoietic stimulating factor, Blood 12:123.PubMedGoogle Scholar
  44. Lorenz, E., Congdon, C., and Uphoff, D., 1952, Modification of acute irradiation injury in mice and guinea pigs by bone marrow injections, Radiology 58:863.PubMedGoogle Scholar
  45. McConnell, I., Hopkins, J., and Lachman, P., 1980, Lymphocyte traffic through lymph nodes during cell shut-down, Ciba Found. Symp. 71:167.PubMedGoogle Scholar
  46. McGhee, J. R., Farrar, J. J., Michalek, S. M., Mergenhagen, S. E., and Rosenstreich, D. L., 1979, Cellular requirements for lipopolysaccharide adjuvanticity: A role for both T lymphocytes and macrophages for in vitro responses to particulate antigens, J. Exp. Med. 149:793.PubMedCrossRefGoogle Scholar
  47. Makinodan, T. M., Kastenbaum, A., and Peterson, W. I., 1962, Radiosensitivity of spleen cells from normal and pre-immunized mice and its significance to intact animals, J. Immunol. 88:31.PubMedGoogle Scholar
  48. Mefferd, R. B., Henkel, D. T., and Loeffer, J. B., 1953, Effect of piromen on survival of irradiated mice, Proc. Soc. Exp. Biol. Med. 83:54.PubMedGoogle Scholar
  49. Metcalf, D., 1971, Acute antigen-induced elevation of serum colony stimulating factor (CSF) levels, Immunology 21:427.PubMedGoogle Scholar
  50. Micklem, H. S., and Loutit, J. F., 1966, Tissue Grafting and Radiation, Academic Press, New York.Google Scholar
  51. Miller, C. P., 1956, The effect of irradiation on natural resistance to infection, Ann. N.Y. Acad. Sci. 66:280.CrossRefGoogle Scholar
  52. Moller, G., Andersson, J., Pohlit, H. and Sjöberg, O., 1973, Quantitation of the number of mitogen molecules activating DNA synthesis in T and B lymphocytes, Clin. Exp. Immunol. 13:89.PubMedGoogle Scholar
  53. Murphy, J. B., and Taylor, H. D., 1918, The lymphocyte in natural and induced resistance to transplants. III. The effect of x-rays on artificially induced immunity,J. Exp. Med. 28:1.PubMedCrossRefGoogle Scholar
  54. Ness, D. B., Smith, S., Talcott, J. A., and Grummet, F. C., 1976, T-Cell requirement for the expression of the lipopolysaccharide adjuvant effect in vivo: Evidence for a T-cell dependent and T-cell independent mode of action, Eur. J. Immunol. 6:650.PubMedCrossRefGoogle Scholar
  55. Newberger, P. E., Hamoka, T., and Katz, D. H., 1974, Potentiation of helper T cell function in IgE antibody responses by bacterial lipopolysaccharide (LPS),J. Immunol. 113:824.Google Scholar
  56. Nowotny, A., 1979, Basic Exercises in Immunochemistory, 2nd ed., pp. 69–72, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  57. Nowotny, A., Behling, U. H., and Chang, H., 1975, Relation of structure to function in bacterial endotoxins. VIII. Biological activities in a polysaccharide-rich fraction,J. Immunol. 115:199.PubMedGoogle Scholar
  58. Ozato, K., Adler, W. H., and Ebert, J. D., 1975, Synergism of bacterial lipopolysaccharides and concanavalin A in the activation of thymic lymphocytes, Cell. Immunol. 17:532.PubMedCrossRefGoogle Scholar
  59. Peius, L. M., and Strausser, H. R., 1977, Prostaglandins and the immune response, Life Sci. 20:903.CrossRefGoogle Scholar
  60. Perkins, E. H., Marcus, S., Gyi, K. K., and Miya, F., 1958, Effect of pyrogen on phagocytic digestion and survival of x-irradiated mice, Radiat. Res. 8:502.PubMedCrossRefGoogle Scholar
  61. Petrov, R. V., 1958, Exogenous infections in radiation sickness, Adv. Mod. Biol. 46:48.Google Scholar
  62. Radvany, R., Neale, N., and Nowotny, A., 1966, Relation of structure to function in bacterial O-antigens. VI. Neutralization of endotoxic O-antigens by homologous O-antibody, Ann. X.Y. Acad. Sci. 133:763.CrossRefGoogle Scholar
  63. Rietschel, E. T., Schade, U., Lüderitz, O., Fisher, H., and Peskar, B. A., 1980, Prostaglandins in endotoxicosis, in: Microbiology 1980 (D. Schlessinger, ed.), American Society for Microbiology, Washington, D.C.Google Scholar
  64. Rowley, D., 1955, Stimulation of natural immunity to Escherichia coli infections: Observations on mice, Lancet 1:232.CrossRefGoogle Scholar
  65. Salvin, S. B., and Smith, R. F., 1959, Delayed hypersensitivity in the development of circulating antibody: The effect of x-irradiation, J. Exp. Med. 109:325.PubMedCrossRefGoogle Scholar
  66. Savage, A. M., 1964, Hematopoietic recovery in endotoxin-treated lethally x-irradiated Bub mice, Radiat. Res. 23:180.PubMedCrossRefGoogle Scholar
  67. Schmidtke, J. R., and Najarian, J. S., 1975, Synergistic effects on DNA synthesis of Phytohemagglutinin or concanavalin A and lipopolysaccharide in human peripheral blood lymphocytes,J. Immunol. 114:742.PubMedGoogle Scholar
  68. Shohat, M., Janossy, G., and Dourmashkin, R. R., 1973, Development of rough endoplasmic reticulum in mouse splenic lymphocyte stimulated by mitogen, Eur. J. Immunol. 3:680.PubMedCrossRefGoogle Scholar
  69. Smith, J. C., 1963, Radiation pneumonitis: A review, Annu. Rev. Respir. Dis. 87:647.Google Scholar
  70. Smith, W. W., Alderman, I. M., and Gillespie, R. F., 1957, Increased survival in irradiated animals treated with bacterial endotoxins, Am. J. Physiol. 191:124.PubMedGoogle Scholar
  71. Smith, W. W., Alderman, I. M., and Gillespie, R. E., 1958a, Hemopoietic recovery induced by bacterial endotoxin in irradiated mice, Am. J. Physiol. 192:549.PubMedGoogle Scholar
  72. Smith, W. W., Alderman, I. M., and Gillespie, R. F., 1958b, Resistance to experimental infections and mobilization of granulocytes in irradiated mice treated with bacterial endotoxins, Am. J. Physiol. 192:263.PubMedGoogle Scholar
  73. Smith, W. W., Alderman, I. M., Gornfield, J., 1961, Granulocyte release by endotoxin in normal and irradiated mice, Am. J. Physiol. 201:396.Google Scholar
  74. Smith, W. W., Brecher, G., Fred, S. and Budd, R. A., 1966, Effect of endotoxin on the kinetics of hemopoietic colony-forming cells in irradiated mice, Radiat. Res. 27:710.PubMedCrossRefGoogle Scholar
  75. Spiers, F. W., 1949, The influence of energy absorption and electron range on dosage in irradiated bone, Br. J. Radiol. 12:521.CrossRefGoogle Scholar
  76. Spitznagel, J. K., and Allison, A. C., 1970, Mode of action of adjuvants: Effects on antibody responses to macrophage-associated bovine serum albumin, J. Immunol. 104:128.PubMedGoogle Scholar
  77. Sultzer, B. M., and Nilsson, B. S., 1972, PPD-tuberculin—A B-cell mitogen, Nature New Biol. 240:198.PubMedGoogle Scholar
  78. Takano, T., and Mizuno, D., 1968, Dynamic state of the spleen cells of mice after administration of the endotoxin of Proteus vulgaris. I. Cellular proliferation after administration of the endotoxin, Jpn. J. Exp. Med. 38:171.PubMedGoogle Scholar
  79. Taliaferro, W. H., Taliaferro, L. G., and Jaroslow, B. N., 1964, Radiation and Immune Mechanisms, Academic Press, New York.Google Scholar
  80. Talmage, D. W., 1955, Effect of ionizing radiation on resistance and infection, Annu. Rev. Microbiol. 9:335.PubMedCrossRefGoogle Scholar
  81. Taylor, H. D., Witherbee, W. D., and Murphy, J. B., 1919, The effect of radiation on the functional capacity of lymphocytes,J. Exp. Med. 29:53.PubMedCrossRefGoogle Scholar
  82. Uchiyama, T., and Jacobs, D. M., 1978, Modulation of immune responses by bacterial lipopolysaccharide (LPS): Cellular basis of stimulatory and inhibitory effects of LPS in the in vitro IgM antibody response to a T-dependent antigen,J. Immunol. 121:2347.PubMedGoogle Scholar
  83. Visakorpi, R., 1972, Effect of irradiation on established delayed hypersensitivity: Suppression of skin reactions, recovery and the effect of cell transfer, Acta Pathol. Microbiol. Scand. 80:132.Google Scholar
  84. Wahl, L. M., Wahl, S. M., Mergenhagen, S. E., and Martin, G. R., 1974, Collagenase production by endotoxin-activated macrophages, Proc. Natl. Acad. Sci. USA 71:3598.PubMedCrossRefGoogle Scholar
  85. Wald, N., Thoma, G. E., and Broun, G., 1962, Hematologic manifestations of radiation exposure in man, Prog. Hematol. 3:1.Google Scholar
  86. Watson, J., Aarden, L., Shaw, J., and Paetkan, V., 1979, Molecular and quantitative analysis of helper T-cell replacing factors on the induction of antigen sensitive B and T lymphocytes,J. Immunol. 122:1633.PubMedGoogle Scholar
  87. Westphal, O., and Lüderitz, O., 1954, Chemische Erforschung von Lipololysacchariden gram negativer Bakterien, Angew. Chem. 66:407.CrossRefGoogle Scholar
  88. Wood, D. D., 1979, Mechanism of action of human B-cell activating factor. I. Comparison of the plaque-stimulating activity with thymocyte stimulating activity, J. Immunol. 123:2400.PubMedGoogle Scholar
  89. Youngner, J. S., and Stinebring, W. R., 1966, Comparison of interferon production in mice by bacterial endotoxin and statolon, Virology 20:310.CrossRefGoogle Scholar
  90. Ziemecki, M., and Webb, D. R., 1976, The regulation of the immune response to T-independent antigens by prostaglandins and B-cells,J. Immunol. 117:2158.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Ulrich H. Behling
    • 1
    • 2
  1. 1.Oyster Creek Nuclear Cenerating StationForked RiverUSA
  2. 2.School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Personalised recommendations