A countermeasure to ameliorate immune dysfunction in in vitro simulated microgravity environment: Role of cellular nucleotide nutrition

  • N. W. Hales
  • K. Yamauchi
  • A. Alicea
  • A. Sundaresan
  • N. R. Pellis
  • A. D. Kulkarni
Articles Cell and Tissue Models

Summary

Considerable evidence suggests that space travelers are immunosuppressed, presumably by microgravity environmental stresses, putting them at risk for adverse effects, such as opportunistic infections, poor wound healing, and cancer. The purpose of this study was to examine the role and mechanisms of nucleotide (NT) supplementation as a countermeasure to obviate immunosuppression during space travel. The in vitro rotary cell culture system, a bioractor (BIO), was used to simulate the effect of microgravity and to isolate the neuroendocrine effects inherent to in vitro models. The splenocytes from normal mice were cultured in BIO and control tissue culture (TC) flasks with and without phytohemagglutinin (PHA) for mitogen assays. The culture medium was then supplemented with various concentrations of a nucleosides-nucleotides mixture (NS+NT), inosine, and uridine. Cytokines interleukin (IL)-1β, IL-2, IL-3, tumor necrosis factor-α, and interferon (IFN)-γ were measured from the supernatant by enzyme-linked immunosorbent assay. In the PHA-stimulated cultures the cellular proliferation in the BIO was significantly decreased as compared with the TC flask cells. BIO-cultured cells in the presence of NS+NT maintained mitogen responses similar to the control TC flask cells. The maintenance of the mitogen response in BIO was observed by the supplementation of uridine and not of inosine. These results are in aggreement with our earlier results from unit gravity experiments that showed that pyrimidines are more effective in pleiogenic immunoprotection to hosts. Cytokines IL-1β, IL-2, and IFN-γ in the BIO supernatants of cells cultured in the presence of NS+NT had a significantly higher response than the control vessel. Thus, supplemental NT, especially pyrimidines, can confer immune protection and enhance cytokine responses during space travel.

Key words

in vitro cultures simulated microgravity cell nutrition nucleotides T cells 

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References

  1. Adjei, A. A.; Yamamoto, S.; Kulkarni, A. D. Nucleic-acids and/or their components: a possible role in immune function. J. Nutr. Sci. Vitaminol. (Tokyo) 41:1–16; 1995a.Google Scholar
  2. Adjei, A. A.; Yamauchi, K.; Al-Mansouri, H. M. S. H.; Chan, Y. C.; Kulkarni, A. D.; Konishi, M.; Yamamoto, S. Dietary nucleosides and nucleotides improve cell-mediated immunity in mice. J. Nutr. Immunol. 4:23–35; 1995b.Google Scholar
  3. Armstrong, J. W.; Kirby-Dobbles, K.; Chapes, S. K. The effects of rM-CSF and rIL-6 therapy on immunosuppressed anti-orthostatically suspended mice. J. Appl. Physiol. 768:968–975; 1995.Google Scholar
  4. Cogoli, A. The effect of hypogravity and hypergravity on cells of the immune system. J. Leukoc. Biol. 54:259–268; 1993.PubMedGoogle Scholar
  5. Cogoli, A.; Bechler, B.; Lorenzi, G. Response of cells to microgravity. In: Asashima, M.; Malacinski, G. M., ed. Fundamentals of space biology. Tokyo; Springer-Japan Science Society Press; 1990:97–111.Google Scholar
  6. Cogoli, A.; Valluchi-Morf, M.; Mueller, M.; Briegleb, W. The effect of hypogravity on human lymphocyte activation. Aviat. Space Environ. Med. 51:29–34; 1980.PubMedGoogle Scholar
  7. Cooper, D.; Pellis, N. R. Suppressed PHA activation of T lymphocytes in simulated microgravity is restored by direct activation of protein kinase C. J. Leukoc. Biol. 63:550–562; 1998.PubMedGoogle Scholar
  8. Konstantinova, I. V.; Rykova, M. P.; Lesnyak, A. T.; Antropova, E. A. Immune changes during long-duration missions. J. Leukoc. Biol. 54:189–201; 1993.PubMedGoogle Scholar
  9. Kulkarni, A. D.; Fanslow, W. C.; Rudolph, F. B.; VanBuren C. T. Effect of dietary nucleotides on response to bacterial infections. J. Parenter. Enter. Nutr. 10:169–171; 1986.Google Scholar
  10. Kulkarni, A. D.; Fanslow, W. C.; Rudolph, F. B.; VanBuren, C. T. Modulation of delayed hypersensitivity in mice by dietary nucleotides. Transplantation 44:847–849; 1987.PubMedGoogle Scholar
  11. Kulkarni, A. D.; Fanslow, W. C.; Rudolph, F. B.; VanBuren, C. T. Immunohemopoietic effects of dietary nucleotide restriction in mice. Transplantation 53:467–472; 1992.PubMedCrossRefGoogle Scholar
  12. Kulkarni, A. D.; Rudolph, F. B.; VanBuren, C. T. The role of dietary source of nucleotides in immune function: a review. J. Nutr. 124:1442S-1446S; 1994.PubMedGoogle Scholar
  13. Kulkarni, A. D.; Yamauchi, K.; Pellis, N. R. Nutrition countermeasure and immune function in microgravity. Proceeding of the 2nd Pan Pacific Basin Workshop on Microgravity, 2001. Pasadena, CA, in press.Google Scholar
  14. Lesnyak, A. T.; Sonnenfeld, G.; Rykova, M. P.; Meshkov, D. O.; Mastro, A.; Konstantinova, I. Immune changes in test animals during spaceflight. J. Leukoc. Biol. 54:214–226; 1993.PubMedGoogle Scholar
  15. Ogoshi, S.; Iwasa, M.; Kitagawa, S. Effect of total parenteral nutrition with nucleoside and nucleotide mixture on d-galactosamine induced liver injury in mice. J. Parenter. Enter. Nutr. 12:53–58; 1988.CrossRefGoogle Scholar
  16. Pellis, N. R.; Goodwin, T. J.; Risin, D.; McIntyre, B. W.; Pizzini, R. P.; Cooper, D.; Baker, T. L.; Spaulding, G. F. Changes in gravity inhibit lymphocyte locomotion through type I collagen. In Vitro Cell. Dev. Biol. 33:398–405; 1997.Google Scholar
  17. Pellis, N. R.; Risin, D.; Sundaresan, A.; Cooper, D. Direct effect of microgravity (MG) on human lymphocytes: functional and morphological aspects. In: ELGRA news, bulletin of the European low gravity research association, vol. 21: 1999:71.Google Scholar
  18. Risin, D.; Prewett, T. L.; Pellis, N. R. Suppression of lymphocyte function in microgravity and potential impact on immunosurveillance [abstract 72]. Anticancer Res. 15(5A):1652: 1995.Google Scholar
  19. Schwarz, R. P.; Goodwin, T. J.; Wolf, D. A. Cell culture for three-dimensional modeling in rotating-wall vessel: an application of simulated microgravity. J. Tissue Cult. Methods 14:51–58; 1992.PubMedCrossRefGoogle Scholar
  20. Taylor, G. R. Overview of spaceflight immunology. J. Leukoc. Biol. 54:179–188; 1993.PubMedGoogle Scholar
  21. Walther, L.; Pippia, P.; Meloni, M. A.; Turrini, F.; Mannu, F.; Cogoli, A. Simulated microgravity inhibits the genetic expression of interleukin-2 and its receptor in mitogens-activated T lymphocytes. FEBS Lett. 436:115–118: 1998.PubMedCrossRefGoogle Scholar

Copyright information

© Society for In Vitro Biology 2002

Authors and Affiliations

  • N. W. Hales
    • 1
  • K. Yamauchi
    • 1
  • A. Alicea
    • 1
  • A. Sundaresan
    • 2
  • N. R. Pellis
    • 3
  • A. D. Kulkarni
    • 1
  1. 1.Department of SurgeryUniversity of Texas Health Science Center-Houston Medical SchoolHouston
  2. 2.Biotechnology, Wyle LaboratoriesHouston
  3. 3.Cellular BiotechnologyJSC/NASAHouston

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