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Modeled microgravity inhibits apoptosis in peripheral blood lymphocytes

  • Special-Nasa/Johnson Space Center Workshop
  • NASA Biotechnology: Cell Science in Microgravity
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Summary

Microgravity interferes with numerous lymphocyte functions (expression of cell surface molecules, locomotion, polyclonal and antigen-specific activation, and the protein kinase C activity in signal transduction). The latter suggests that gravity may also affect programmed cell death (PCD) in lymphocyte populations. To test this hypothesis, we investigated spontaneous, activation- and radiation-induced PCD in peripheral blood mononuclear cells exposed to modeled microgravity (MMG) using a rotating cell culture system. The results showed significant inhibition of radiation- and activation-induced apoptosis in MMG and provide insights into the potential mechanisms of this phenomenon.

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References

  • Alderson, M. R.; Tough, T. W.; Davis-Smith T., et al. Fas ligand mediates activation-induced cell death in human T lymphocytes. J. Exp. Med. 181:71–77; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Belka, C.; Marini, P.; Budach, W., et al. Radiation-induced apoptosis in human lymphocytes and lymphoma cells critically relies on the upregulation of CD95/Fas/APO-1 ligand. Radial. Res. 149:588–595; 1998.

    Article  CAS  Google Scholar 

  • Brunner, T.; Mogil, R. J.; LaFace, D., et al. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373:441–444; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Brunner, T.; Yoo, N. J.; Griffith, T. S., et al. Regulation of CD95 ligand expression: a key element in immune regulation. Behring Inst. Mitt. 97:161–174; 1996.

    PubMed  CAS  Google Scholar 

  • Chao, D. T.; Korsmeyer, S. J. BCL-2 family: regulators of cell death. Ann. Rev. Immunol. 16:395–419; 1998.

    Article  CAS  Google Scholar 

  • Cheng, E. H.; Levine, B.; Boise, L. H., et al. Bax-indpendent inhibition of apoptosis by Bcl-XL. Nature 379:554–556; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Cogoli, A. The effect of hypogravity and hypergravity on cells of the immune system. J. Leukoc. Biol. 54:259–268; 1993.

    PubMed  CAS  Google Scholar 

  • Cogoli, A.; Bechler, B.; Cogoli-Greuter, M., et al. Microgenic signal transduction in T lymphocytes in microgravity. J. Leukoc. Biol. 53:569–575; 1993.

    PubMed  CAS  Google Scholar 

  • 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 

  • Cogoli, A.; Bechler, B.; Muller, O.; Hunzinger, E. Effect of microgravity on lymphocyte activation. In: Longdon, N.; David, V., ed. Biorack on Spacelab D1. ESA SP-1091, ESTEC, Noordwijk: ESA Publications Division; 1988:89–100.

    Google Scholar 

  • Cogoli, A.; Tschopp, A. Lymphocyte reactivity during spaceflight. Immunol. Today 6:1–4; 1985.

    Article  PubMed  CAS  Google Scholar 

  • Cogoli, A.; Tschopp, A.; Fuchs-Bislin, P. Cell sensitivity to gravity. Science 225:228–230; 1984.

    Article  PubMed  CAS  Google Scholar 

  • Cogoli, A.; Valluchi-Morf, M.; Muller, M., et al. The effect of hypogravity on human lymphocyte activation. Aviat. Space Environ. Med. 51:29–34; 1980.

    PubMed  CAS  Google Scholar 

  • Congdon, C. C.; Allebban, Z.; Gibson, L. A. et al. Lymphatic tissue changes in rats flown on Spacelab Life Sciences-2. J. Appl. Physiol. 81:172–177; 1996.

    PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • Delic, J.; Morange, M.; Magdelenat, H. Ubiquitin pathway involvement in human lymphocyte ψ-irradiation-induced apoptosis. Mol. Cell. Biol. 13:4875–4883; 1993.

    PubMed  CAS  Google Scholar 

  • Dhein, J.; Walczak, H.; Baumler, C., et al. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature 373:438–441; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Goodwin, T. J.; Prewett, T. L.; Wolf, D. A., et al. Reduced shear stress: a major component in the ability of mammalian tissues to form three-dimensional assemblies in simulated microgravity. J. Cell. Biochem. 51:301–311; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Jessup, J. M.; Goodwin, T. J.; Spaulding, G. F. Prospects for use of microgravity-based bioreactors to study three-dimensional host-tumor interactions in human neoplasia. J. Cell. Biochem. 51:290–300; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Ju, S.-T.; Panka, D. J.; Cui, H., et al. Fas (CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373:444–448; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Korsmeyer, S. J.; Shutter, J. R.; Veis, D. J., et al. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin. Cancer Biol. 4:327–332; 1993.

    PubMed  CAS  Google Scholar 

  • Krammer, P. H. CD95(APO-1/Fas)-mediated apoptosis: live and let die. Adv. Immanol. 71:163–210; 1999.

    Article  CAS  Google Scholar 

  • Lewis, M. L.; Reynolds, J. L.; Cubano, L. A., et al. Spaceflight alters micro-tubules and increases apoptosis in human lymphocytes (Jurkat). FASEB J. 12:1007–1018; 1998.

    PubMed  CAS  Google Scholar 

  • Muller, H. K.; Bucana, C. D.; Kripke, M. L. et al. Ultraviolet irradiation of murine skin alters cluster formation between lymph node dendritic cells and specific T lymphocytes. Cell. Immunol. 157:263–276; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Nicoletti, I.; Migliorati, G.; Pagliacci, M. C., et al. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immunol. Methods 139:271–279; 1991.

    Article  PubMed  CAS  Google Scholar 

  • Oltvai, Z. N.; Korsmeyer, S. J. Checkpoints of dueling dimers foil death wishes. Cell 79:189–192; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Oltvai, Z. N.; Milliman, C. L.; Korsmeyer, S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74:609–619; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Pellis, N. R.; Goodwin, T. J.; Risin, D., et al. Changes in gravity inhibit lymphocyte locomotion through type 1 collagen. In Vitro Cell. Dev. Biol. 33A:398–405; 1997.

    Google Scholar 

  • Pellis, N. R.; Risin, D.; Sundaresan, A.; Cooper, D. Direct effect of microgravity (MC) on human lymphocytes: functional and morphological aspects. In: ELGRA news, bulletin of the European low gravity research association, Vol. 21; 1999:71.

  • Reed, J. C. Bel-2 and the regulation of programmed cell death. J. Cell. Biol. 124:1–6; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Reed, J. C. Bcl-2 family proteins. Oncogene 17:3225–3236; 1998.

    Article  PubMed  Google Scholar 

  • 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 

  • Schwarz, R. P.; Goodwin, T. J.; Wolf, D. A. Cell culture for three-dimensional modeling in rotating-wall vessels: an application in simulated microgravity. J. Tissue Cult. Methods 14:51–58; 1992.

    Article  PubMed  CAS  Google Scholar 

  • Sedlak, T. W.; Oltvai, Z. N.; Yang, E., et al. Multiple Bcl-2 family members demonstrate selective dimerization with Bax. Proc. Natl. Acad. Sci. USA 92:7834–7838; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Seki, H.; Kanegane, H.; Iwai, K., et al. Ionizing radiation induces apoptotic cell death in human TCr-γ/δ+ and natural killer cells without detectable p53 protein. Eur. J. Immunol. 24:2914–2917; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Singer, G. G.; Abbas, A. K. The Fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity 1:365–371; 1994.

    Article  PubMed  CAS  Google Scholar 

  • Taylor, G. R. Overview of spaceffight immunology studies. J. Leukoc. Biol. 54:179–188; 1993.

    PubMed  CAS  Google Scholar 

  • Tsao, Y. D.; Goodwin, T. J.; Wolf, D. A.; Spaulding, G. F. Responses of gravity level variations on the NASA/JSC bioreactor system. The Physiologist 35:S49-S50; 1992.

    PubMed  CAS  Google Scholar 

  • Van Parijs, L.; Ibraghimov, A.; Abbas, A. K. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity 4:321–328; 1996.

    Article  PubMed  Google Scholar 

  • Walther, I.; Pippia, P.; Meloni, M. A., et al. Simulated microgravity inhibits the genetic expression of interleukin-2 and its receptor in mitogen-activated T lymphocytes. FEBS Lett. 436:115–118; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Hin, X. M.; Oltvai, Z. N.; Korsmeyer, S. J. BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. Nature 369:321–323; 1994.

    Article  Google Scholar 

  • Zamzami, N.; Brenner, C.; Marzo, I., et al. Subcellular and submitochondrial mode of action of Bcl-2-like oncoproteins Oncogene 16:2265–2282; 1998.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Biotechnology Program, Wyle Laboratories-Life Sciences, Systems and Services, 2101 NASA Road 1, 77058, Houston, TX

    Neal R. Pellis

  2. Cellular Biotechnology Program, NASA-Johnson Space Center, 2101 NASA Road 1, 77058, Houston, TX

    Diana Risin

Authors
  1. Diana Risin
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  2. Neal R. Pellis
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Correspondence to Diana Risin.

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Risin, D., Pellis, N.R. Modeled microgravity inhibits apoptosis in peripheral blood lymphocytes. In Vitro Cell.Dev.Biol.-Animal 37, 66–72 (2001). https://doi.org/10.1290/1071-2690(2001)037<0066:MMIAIP>2.0.CO;2

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  • DOI: https://doi.org/10.1290/1071-2690(2001)037<0066:MMIAIP>2.0.CO;2

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