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. 1986 Jan;51(1):87–93. doi: 10.1128/iai.51.1.87-93.1986

Antimicrobial activity of various immunomodulators: independence from normal levels of circulating monocytes and natural killer cells.

P S Morahan, W L Dempsey, A Volkman, J Connor
PMCID: PMC261069  PMID: 2416693

Abstract

The effects of 89Sr treatment on the natural host resistance of CD-1 mice and the enhancement of resistance by immunomodulators to infection with Listeria monocytogenes or herpes simplex virus type 2 (HSV-2) were determined. In the CD-1 mouse, single-dose treatment with 89Sr caused a profound decrease in the number of circulating monocytes (Mo), lymphocytes, and polymorphonuclear leukocytes (PMN) within 1 week. There was also marked functional impairment of the Mo inflammatory response, as well as markedly decreased spontaneous and activatable cytotoxicity by splenic natural killer (NK) cells. Despite this profound cellular suppression, there was no significant change in natural resistance of CD-1 mice to L. monocytogenes or HSV-2 infection. Furthermore, prophylactic treatment of mice with the biologic immunomodulator Corynebacterium parvum or the synthetic immunomodulators maleic anhydride-divinyl ether or avridine in liposomes resulted in comparable enhancement of resistance in 89Sr-treated and normal mice. These data indicate that natural and immunomodulator-enhanced resistance of CD-1 mice to microbial infections do not depend on normal levels of Mo, PMN, or NK cells. The resistance enhancement may rely on activated tissue macrophages (M phi). In contrast to the early changes in circulating leukocytes, the resident peritoneal cell populations were not markedly altered until after day 30. There then was a distinct decline in lymphocytes and a gradual decline in M phi; the change in M phi was apparently due to the lack of an age-related increase in the peritoneal M phi population in 89Sr-treated mice in comparison with a slight increase in resident M phi in normal mice. After CD-1 mice were treated with 89Sr, the number of PMN and the function of NK cells generally recovered by about day 50 and was followed by partial recovery of circulating Mo, unless a second dose of 89Sr was administered.

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Selected References

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  1. Adler S. S., Trobauch F. E., Jr, Knospe W. H. Hemopoietic stem cell dynamics in 89Sr marrow-ablated mice. J Lab Clin Med. 1977 Mar;89(3):592–602. [PubMed] [Google Scholar]
  2. Bennett M., Baker E. E., Eastcott J. W., Kumar V., Yonkosky D. Selective elimination of marrow precursors with the bone-seeking isotope 89Sr: implications for hemopoiesis, lymphopoiesis, viral leukemogenesis and infection. J Reticuloendothel Soc. 1976 Jul;20(1):71–87. [PubMed] [Google Scholar]
  3. Bennett M., Baker E. E. Marrow-dependent cell function in early stages of infection with Listeria monocytogenes. Cell Immunol. 1977 Sep;33(1):203–210. doi: 10.1016/0008-8749(77)90147-2. [DOI] [PubMed] [Google Scholar]
  4. Bennett M., Kumar V. 89Sr-induced bone marrow aplasia: effects on seed (stem cells) and soil (inductive microenvironment). Lab Invest. 1983 Sep;49(3):235–236. [PubMed] [Google Scholar]
  5. Coggle J. E., Tarling J. D. The proliferation kinetics of pulmonary alveolar macrophages. J Leukoc Biol. 1984 Mar;35(3):317–327. doi: 10.1002/jlb.35.3.317. [DOI] [PubMed] [Google Scholar]
  6. Habu S., Fukui H., Shimamura K., Kasai M., Nagai Y., Okumura K., Tamaoki N. In vivo effects of anti-asialo GM1. I. Reduction of NK activity and enhancement of transplanted tumor growth in nude mice. J Immunol. 1981 Jul;127(1):34–38. [PubMed] [Google Scholar]
  7. Haller O., Wigzell H. Suppression of natural killer cell activity with radioactive strontium: effector cells are marrow dependent. J Immunol. 1977 Apr;118(4):1503–1506. [PubMed] [Google Scholar]
  8. Kumar V., Ben-Ezra J., Bennett M., Sonnenfeld G. Natural killer cells in mice treated with 89strontium: normal target-binding cell numbers but inability to kill even after interferon administration. J Immunol. 1979 Oct;123(4):1832–1838. [PubMed] [Google Scholar]
  9. Kumar V., Luevano E., Bennett M. Hybrid resistance to EL-4 lymphoma cells. I. Characterization of natural killer cells that lyse EL-4 cells and their distinction from marrow-dependent natural killer cells. J Exp Med. 1979 Sep 19;150(3):531–547. doi: 10.1084/jem.150.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lopez C. Genetics of natural resistance to herpesvirus infections in mice. Nature. 1975 Nov 13;258(5531):152–153. doi: 10.1038/258152a0. [DOI] [PubMed] [Google Scholar]
  11. Lopez C., Ryshke R., Bennett M. Marrow-dependent cells depleted by 89Sr mediate genetic resistance to herpes simplex virus type 1 infection in mice. Infect Immun. 1980 Jun;28(3):1028–1032. doi: 10.1128/iai.28.3.1028-1032.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mandel T. E., Cheers C. Resistance and susceptibility of mice to bacterial infection: histopathology of listeriosis in resistant and susceptible strains. Infect Immun. 1980 Dec;30(3):851–861. doi: 10.1128/iai.30.3.851-861.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Masuda A., Bennett M. Murine cytomegalovirus stimulates natural killer cell function but kills genetically resistant mice treated with radioactive strontium. Infect Immun. 1981 Dec;34(3):970–979. doi: 10.1128/iai.34.3.970-979.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McGeorge M. B., Morahan P. S. Comparison of various macrophage-inhibitory agents on vaginal and systemic herpes simplex virus type 2 infections. Infect Immun. 1978 Nov;22(2):623–626. doi: 10.1128/iai.22.2.623-626.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mellen P. F., Lust J. A., Bennett M., Kumar V. Analysis of low natural killer cell activity in 89Sr-treated mice. Eur J Immunol. 1982 May;12(5):442–445. doi: 10.1002/eji.1830120516. [DOI] [PubMed] [Google Scholar]
  16. Morahan P. S., Barnes D. W., Munson A. E. Relationship of molecular weight to antiviral and antitumor activities and toxic effects of maleic anhydride-divinyl ether (MVE) polyanions. Cancer Treat Rep. 1978 Nov;62(11):1797–1803. [PubMed] [Google Scholar]
  17. Morahan P. S., Bradley S. G., Munson A. E., Duke S., Fromtling R. A., Marciano-Cabral F. Immunotoxic effects of diethylstilbestrol on host resistance: comparison with cyclophosphamide. J Leukoc Biol. 1984 Mar;35(3):329–341. doi: 10.1002/jlb.35.3.329. [DOI] [PubMed] [Google Scholar]
  18. Morahan P. S., Coleman P. H., Morse S. S., Volkman A. Resistance to infections in mice with defects in the activities of mononuclear phagocytes and natural killer cells: effects of immunomodulators in beige mice and 89Sr-treated mice. Infect Immun. 1982 Sep;37(3):1079–1085. doi: 10.1128/iai.37.3.1079-1085.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morahan P. S., Connor J. R., Leary K. R. Viruses and the versatile macrophage. Br Med Bull. 1985 Jan;41(1):15–21. doi: 10.1093/oxfordjournals.bmb.a072017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morahan P. S., Edelson P. J., Gass K. Changes in macrophage ectoenzymes associated with anti-tumor activity. J Immunol. 1980 Sep;125(3):1312–1317. [PubMed] [Google Scholar]
  21. Niblack J. F., Otterness I. G., Hemsworth G. R., Wolff J. S., 3rd, Hoffman W. W., Kraska A. R. CP-20,961: a structurally novel, synthetic adjuvant. J Reticuloendothel Soc. 1979 Dec;26(Suppl):655–666. [PubMed] [Google Scholar]
  22. Perkins E. H., Massucci J. M., Glover P. L. Antigen presentation by peritoneal macrophages from young adult and old mice. Cell Immunol. 1982 Jun;70(1):1–10. doi: 10.1016/0008-8749(82)90128-9. [DOI] [PubMed] [Google Scholar]
  23. Santoni A., Puccetti P., Riccardi C., Herberman R. B., Bonmassar E. Augmentation of natural killer activity by pyran copolymer in mice. Int J Cancer. 1979 Nov 15;24(5):656–661. doi: 10.1002/ijc.2910240520. [DOI] [PubMed] [Google Scholar]
  24. Sawyer R. T., Strausbauch P. H., Volkman A. Resident macrophage proliferation in mice depleted of blood monocytes by strontium-89. Lab Invest. 1982 Feb;46(2):165–170. [PubMed] [Google Scholar]
  25. Stein-Streilein J., Bennett M., Mann D., Kumar V. Natural killer cells in mouse lung: surface phenotype, target preference, and response to local influenza virus infection. J Immunol. 1983 Dec;131(6):2699–2704. [PubMed] [Google Scholar]
  26. Tarling J. D., Coggle J. E. The absence of effect on pulmonary alveolar macrophage numbers during prolonged periods of monocytopenia. J Reticuloendothel Soc. 1982 Mar;31(3):221–224. [PubMed] [Google Scholar]
  27. Volkman A., Chang N. C., Strausbauch P. H., Morahan P. S. Differential effects of chronic monocyte depletion on macrophage populations. Lab Invest. 1983 Sep;49(3):291–298. [PubMed] [Google Scholar]
  28. van Furth R. Macrophage activity and clinical immunology. Origin and kinetics of mononuclear phagocytes. Ann N Y Acad Sci. 1976;278:161–175. doi: 10.1111/j.1749-6632.1976.tb47027.x. [DOI] [PubMed] [Google Scholar]

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