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Lipid A of Salmonella typhimurium Suppressed T-cell Mitogen-Induced Proliferation of Murine spleen Cells in the Presence of Macrophage

Salmonella typhimurium lipid A를 처리한 식세포 존재 조건에서 mitogen에 유도되는 이자 세포의 증식억제

  • Kang, Gyong-Suk (Department of Family Medicine, Daehan-Wellness Hospital) ;
  • Chung, Kyung-Tae (Department of Life Science and Biotechnology, Dong-Eui University)
  • Published : 2007.01.29

Abstract

Infection with virulent or attenuated Salmonella typhimuriumhas known to induce reduction in proliferative responses of spleen cells. We investigated a role of lipid A from S. typhimurium, a B cell mitogen, on proliferation of spleen cells by T cell mitogens such as concanavaline A and phytohemagglutinin under in vitro and ex vivo conditions. Lipid A alone induced proliferation of spleen cells in vitroin a dose-dependent manner. However, subsequent treatment of concanavaline A or phytohemagglutin in after lipid A treatment induced proliferation suppression of murine spleen cells in vitro and ex vivo. Removal of macrophages from spleen cells, which were obtained from a lipid A-injected mouse, restored proliferation by concanavaline A and phytohemagglutinin, indicating that macrophages appeared to play a role in lipid A-induced suppression. Secreted molecules from macrophages did not accounted for the suppression because suppressive effect was not achieved when the supernatant from macrophage-containing spleen cell culture was conditoned to macrophage-depleted spleen cell culture. Co-culture of spleen cells from lipid A-treated and - untreated mice showed proliferation suppression as increasing cell numbers of lipid A-treated mouse. These data suggested that the cell-to-cell contact of macrophage with splenic lymphocyte cells is responsible for immune responses against lipid A, which is applicable to the case of human S. typhi infection.

사람의 장티푸스 연구는 생쥐에 감염되는 Salmonella typhimurium를 모델로 연구되고 있으며, 생쥐에 있어서 S. typhimurium의 감염은 이자세포의 증식반응을 감소시키는 것으로 알려져 있다. S. typhimurium lipid A의 처리가 T세포 mitogen에 의한 이자 세포의 증식에 어떤 영향을 주는 가를 in vitro와 ex vivo조건에서 알아 보았다. Lipid A 단독 처리는 이자 세포의 증식을 보였으나, lipid A 처리 후 T 세포 mitogen인 concanavalin A (Con A)와 phytohemagglutinin (PHA)에 의한 in vitro와 ex vivo 조건에서의 이차 처리는 오히려 세포증식이 억제되었다. Lipid A를 주사한 생쥐로부터 분리한 이자 세포에서 대식세포를 제거하였을 조건에서는 T 세포 mitogen에 의한 증식 효과가 유지되었으나 대식세포를 제거하지 않았을 경우에는 T세포 mitogen에 의한 증식 효과가 억제되었다. Lipid A를 주사한 생쥐에서 얻은 대식세포를 포함한 이자세포의 숫자를 증가하면서 Lipid A를 주사하지 않은 생쥐에서 얻은 이자세포와 혼합 배양하였을 때 Lipid A를 주사한 생쥐에서 얻은 대식세포를 포함한 이자세포의 숫자가 높을수록 Con A와 PHA에 의한 증식억제가 높게 측정되었다. 이러한 결과는 Con A와 PHA의 이자세포 증식 기능이 lipid A의 전처리에 의해 활성화된 대식세포의 직접적인 접촉 작용으로 억제된 것으로 생각된다. 본 연구의 결과를 바탕으로 억제에 관여하는 대식세포 표면분자를 밝히는 것이 사람의 장티푸스 연구에 도움이 되리라 생각된다.

Keywords

References

  1. Albina, J. E., J. A. Abata and W. L Henry Jr,. 1991.Nitric oxide production is required for murine resident macrophages to suppress mitogen-stimulated T-cell proliferation. J. Immunol. 147, 144-148
  2. Al-Ramadi, B. K., J. M. Greene, J. J. Meissler Jr. and T. K Eisenstein. 1992. Immunsuppression induced by attenuated Salmonella; effect of LPS responsiveness on development of suppression. Microb. Pathog. 12, 267-278 https://doi.org/10.1016/0882-4010(92)90045-P
  3. Andersson, J., G. M. Edelman, G. Moeller and O. Sjerberg. 1972. Activation of B lymphocytes by locally concentrated concanavalin A. Eur. J. Immunol. 2, 233-235 https://doi.org/10.1002/eji.1830020307
  4. Anne, T. M. and C. W. Pierce. 1981. Conversion of soluble immune response suppressor to macrophage-derived suppressor factor by peroxide. Proc. Natl. Acd. Sci. 78, 5099-5103 https://doi.org/10.1073/pnas.78.8.5099
  5. Bloembergen P, F. M. Hofhuis, C. Hol and H. van Dijk. 1990. Endotoxin-induced auto-immunity in mice. III. Comparison of different endotoxin preparations. Int. Arch. Allergy Appl. Immunol. 92, 124-130 https://doi.org/10.1159/000235202
  6. Brunner, H. and H. P. Kroll. 1989. Reduced proliferative response of mouse spleen cells to mitogens during infection with Salmonella typhimurium or Listeria monocytogeneses. Micro. Pathog. 6, 265-276 https://doi.org/10.1016/0882-4010(89)90100-9
  7. Caroff, M., D. Karibian, J. M. Cavaillon and N. Haeffner-Cavaillon. 2002. Structural and functional analyses of bacterial lipopolysaccaharides. Microbes Infect. 4, 915-926 https://doi.org/10.1016/S1286-4579(02)01612-X
  8. Collins, F. M. 1974. Vaccins and cell-mediated immunity. Bacteriol. Rev. 38, 371-402
  9. Eisenstein, T. K. and B. M. Sultzer, 1983. Immunity to Salmonella infection. Adv. Exp. Med. Biol. 162, 261-296 https://doi.org/10.1007/978-1-4684-4481-0_26
  10. Elliot, L., W. Brooks and T. Roszman. 1993. Inhibition of anti-CD3 monoclonal antibody-induced T-cell proliferation and interleukin-2 secretion by physiologic combinations of dexamethasone and prostaglandin E2. Cell. Mol. Neurobiol. 13, 579-592 https://doi.org/10.1007/BF00711558
  11. Erridge, C., E. Bennett-Guerro and I. R. Poxton, 2002. Structure and function of lipopolysaccharides. Microbes Infect. 4, 837-851 https://doi.org/10.1016/S1286-4579(02)01604-0
  12. Howard, M. and A. O'Garra. 1992. Biological properties of interleukin 10. Immunol. Today 13, 198-200 https://doi.org/10.1016/0167-5699(92)90153-X
  13. Huang, D., M. G. Schwacha and T. K. Eisenstein. 1996. Attenuated Salmonella vaccine-induced suppression of murine spleen cell responses to mitogen is mediated by macrophage nitric oxide quantitative aspects. Infect. Immunol. 64, 3786-3792
  14. Johnson, R. B., S. Kohl and W. G. Bessler. 1983. Polyclonal activayion of B-lymphocytes in vivo by Salmonella typhimurium lipoprotein. Infect. Immunol. 39, 1481-1484
  15. Khan, I. A., T. Matsuura and L. H. Kasper. 1996. Activation-mediated CD4+ T cell unresponsiveness during acute Toxoplasma gondii infection in mice. Int. Immunol. 8, 887-896 https://doi.org/10.1093/intimm/8.6.887
  16. Lissner, R. C., R. N. Swanson and A. D. Oberien, 1983. Genetic control of the innate resistance of the Ity gene in peritoneal and splenic macrophages isolated in vitro. J. Immunol. 131, 3006-3013
  17. Luderitz, O. M., C. Freudenberg, V. Galanos, E. T. Lehmann and D. H. Rietschel, 1982. Lipopolysaccharides of gram-negative bacteria. Curr. Top. Membr. Transp. 17, 79-151 https://doi.org/10.1016/S0070-2161(08)60309-3
  18. Ly, I. A. and R. L. Michell. 1974. Separation of mouse spleen cells by passage through colums of sephadex G-10. J. Immunol. Methods. 5, 239-247 https://doi.org/10.1016/0022-1759(74)90108-2
  19. Matsui, K. and T. Arai. 1993. Inhibition of mitogen-induced proliferation of spleen lymphocytes is correlated with the reduction of cell mediated immunity in Salmonella infection in mice. FEMS. Microbiol. Lett. 112, 113-118 https://doi.org/10.1111/j.1574-6968.1993.tb06432.x
  20. Matsui, K. and T. Arai. 1994. Cell-free extract of Salmonella inhibits mitogen-induced proliferation of murine splenic T-lymphocytes. FEMS. Immunol. Med. Microbiol. 8, 141-150 https://doi.org/10.1111/j.1574-695X.1994.tb00436.x
  21. Matsui, K. and T. Arai. 1998. Salmonella infection-induced non-responsiveness of murine splenic T-lymphocytes to interleukin-2 (IL-2) involves inhibition of IL-2 receptor gamma chain expression. FEMS. Immunol. Med. Microbiol. 20, 175-180 https://doi.org/10.1111/j.1574-695X.1998.tb01125.x
  22. Metzger, Z., J. T. Hoffeld and J. J. Oppenheim. 1980. Macrophage-mediated suppression. I. Evidence for participation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte responses. J. Immunol. 124, 983-988
  23. Nabeshima, S., M. Nomoto, G. Matsuzaki, K. Kishihara, H. Taniguchi, S. I. Yoshida and K. Nomoto. 1999. T-cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis. Infect .Immun. 67, 3221-3226
  24. Peavy, D. L., J. W Shands, W. H. Adler and R T. Smith. 1973. Mitogenicity of bacterial endotoxins: characterization of the mitogenic principle. J. Immunol. 111, 352-357
  25. Perera, P. Y., T. N. Mayadas, O. Takeuchi, S. Akira, M. Zaks-Zilberman, S. M. Goyert and S. N. Vogel. 2001. CD11b/CD18 acts in concert with CD14 and Toll-like receptor(TLR)4 to elicit full lipopolysaccharide and taxol-inducible gene expression. J. Immunol. 166, 574-581 https://doi.org/10.4049/jimmunol.166.1.574
  26. Poltorak, A., X. He, I. Smirnova, M.Y. Liu, C. Van Huffel, X. Du, D. Birdwell, E. Alejos, M. Silva, C. Galanos, M. Freudenberg, P. Ricciardi-Castagnoli, B. Layton and B. Beutler. 1998. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science, 282, 2085-2088 https://doi.org/10.1126/science.282.5396.2085
  27. S. T. Qureshi, L. Lariviere, G. Leveque, S. Clermont, K. J. Moore, P. Gros and D. Malo. 1999. Endotoxin-tolerant mice have mutations in toll-like receptor 4 (Tlr4). J. Exp. Med. 189, 615-625 https://doi.org/10.1084/jem.189.4.615
  28. Schumann, R. R., S. R. Leong, G. W. Flaggs, P. W. Gray, S. D. Wright, J. C. Mathison and R. J. Ulevitch. 1990. Structure and function of lipopolysaccharide binding protein Science, 249, 1429-1431 https://doi.org/10.1126/science.2402637
  29. Schwacha, M. G., J. J. Meissler Jr. and T. K. Eisenstein, 1998. Salmonella typhimurium infection in mice induces nitric oxide-mediated immunosuppreassion through a natural killer cell-dependent pathway. Infect. Immunol. 66, 5862-5866
  30. Sergeva, M. G., M. V. Gonchas, A. T. Mevkeh and S. D. Varfolomeyev. 1997. Prostaglandin E2 biphasic control of lymphocyte proliferation, inhibition by picomolar concentrations. FEBS. Lett. 418, 235-238 https://doi.org/10.1016/S0014-5793(97)01388-4
  31. Shimizu, T., C. Sano and H. Tomioka. 2004. The role of B7 molecules in the cell contact-mediated suppression of T cell mitogenesis by immunosuppressive macrophages induced with mycobacterial infection. Clin. Exp. lmmunol. 135, 373-379 https://doi.org/10.1111/j.1365-2249.2004.02403.x
  32. Stickland, D., U. R. Kees and P. G. Holt. 1996. Regulation of T-cell activation in the lung alveolar macrophages induce reversible T-cell anergy in vitro associated with inhibition of interleukin-2 receptor signal transduction. Immunology, 87, 250-258 https://doi.org/10.1046/j.1365-2567.1996.459542.x
  33. Sultzer, B. M. and G. Goodman. 1976. Endotoxin protein: a B cell mitogen and polyclonal activator of C3H/HeJ lymphocytes. J. Exp. Med. 144, 821-827 https://doi.org/10.1084/jem.144.3.821
  34. Tomioka, H and H. Saito. 1992. Immunosuppressive macrophages induced in Mycobacterium avium complex infection induced in mice. Kekkaku. 67, 47-54. (Japanese)
  35. Wright, S. D., R. A. Ramos, P. S. Tobias, R. J. Ulevitch and J. C. Mathison. 1990. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science, 249, 1431-1433 https://doi.org/10.1126/science.1698311