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The Differential Immunomodulating Effects of Levan and DFA-IV on Macrophage Function

  • Park, Sul-Kyoung (Department of Herbal Medicine Resource, Kangwon National University) ;
  • Jang, Ki-Hyo (Department of Food and Nutrition, Kangwon National University) ;
  • Kim, Mi-Hyun (Department of Food and Nutrition, Kangwon National University) ;
  • Lim, Jung-Dae (Department of Herbal Medicine Resource, Kangwon National University) ;
  • Han, Eun-Tek (Department of Parasitology, College of Medicine, Kangwon National University) ;
  • Jang, Seon-A (Department of Herbal Medicine Resource, Kangwon National University) ;
  • Kim, Kyung-Ho (College of Pharmacy, Sungkyunkwan University) ;
  • Pyo, Suhk-Neung (College of Pharmacy, Sungkyunkwan University) ;
  • Sohn, Eun-Hwa (Department of Herbal Medicine Resource, Kangwon National University)
  • Published : 2008.03.31

Abstract

Di-D-fructose-2,6':6,2'-dianhydride (DFA-IV) is a disaccharide consisting of two fructose residues that are prepared from levan by levan fructotransferase. Levan is a homopolysaccharide composed of D-fructofuranosyl residues joined by $\beta$-(2,6) and $\beta$-(2,1) linkages. We compared the immunomodulatory effects of levan with DFA-IV. Tumoricidal activity, phagocytosis and nitric oxide (NO) production were examined in levan- and DFA-IV-treated RAW264.7 cells. The NO production, tumoricidal and phagocytic activities were significantly increased in both treated cells. The results indicate that levan has significantly greater effects on tumoricidal activity than DFA-IV at low concentrations (1 ${\mu}g/mL$) and its effect on NO production shows a similar pattern. These results suggest that tumoricidal activity induced by both samples is mediated by NO production.

References

  1. Han YW. 1989. Levan production by Bacillus polymyxa. J Ind Microbiol 4: 447-452 https://doi.org/10.1007/BF01569641
  2. Saito K, Tomita F. 2000. Difructose anhydrides: their mass-production and physiological functions. Biosci Biotechnol Biochem 64: 1321-1327 https://doi.org/10.1271/bbb.64.1321
  3. Han YW. 1990. Microbial levan. Adv Appl Microbiol 35: 171-194 https://doi.org/10.1016/S0065-2164(08)70244-2
  4. Jang KH, Ryu EJ, Park BS, Song KB, Kang SA, Kim CH, Uhm TB, Park YI, Rhee SK. 2003. Levan fructotrasferase from Arthrobacter oxydans J17-21 catalyzes the formation of the di-D-fructose dianhydride IV from levan. J Agric Food Chem 51: 2632-2636 https://doi.org/10.1021/jf026207o
  5. Song KB, Bae KS, Lee YB, Lee KY, Rhee SK. 2000. Characteristics of levan fructotransferase from Arthrobacter ureafaciens K2032 and difructose anhydride IV formation from levan. Enzyme Microb Technol 27: 212-218 https://doi.org/10.1016/S0141-0229(00)00135-6
  6. Kim CH, Jang EK, Kim SH, Jang KH, Kang SA, Song KB, Kwon OS, Rhee SK. 2005. Molecular cloning of levan fructotransferase gene from Arthrobacter ureafaciens K2032 and its expression in Escherichia coli for the production of difructose dianhydride IV. Lett Appl Microbiol 40: 228-234 https://doi.org/10.1111/j.1472-765X.2005.01658.x
  7. Xu Q, Yajima T, Li W, Saito K, Ohshima Y, Yoshikai Y. 2006. Levan (beta-2, 6-fructan), a major fraction of fermented soybean mucilage, displays immunostimulating properties via Toll-like receptor 4 signalling: induction of interleukin-12 production and suppression of T-helper type 2 response and immunoglobulin E production. Clin Exp Allergy 36: 94-101 https://doi.org/10.1111/j.1365-2222.2006.02401.x
  8. Hahn H, Kaufmann SH. 1981. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis 3: 1221-1250 https://doi.org/10.1093/clinids/3.6.1221
  9. Verstovsek S, Maccubbin D, Ehrke MJ, Mihich E. 1992. Tumoricidal activation of murine resident peritoneal macrophages by interleukin 2 and tumor necrosis factor alpha. Cancer Res 52: 3880-3885
  10. Adams DO, Hamilton TA. 1984. The cell biology of macrophage activation. Annu Rev Immunol 2: 283-318 https://doi.org/10.1146/annurev.iy.02.040184.001435
  11. Burleson GR, Dean JH, Munson AE. 1995. Introduction to the mononuclear phagocyte system. In Methods in immunotoxicology. Wiley-Liss, New York, USA. Vol 2, p 3-13
  12. Nathan CF. 1987. Secretory products of macrophages. J Clin Invest 79: 319-326. https://doi.org/10.1172/JCI112815
  13. Fidler IJ, Kleinerman ES. 1983. Therapy of cancer metastasis by systemic activation of macrophages: from the bench to the clinic. Res Immunol 144: 284-287 https://doi.org/10.1016/0923-2494(93)80109-C
  14. Keller R, Keist R. 1989. Abilities of activated macrophages to manifest tumoricidal activity and to generate reactive nitrogen intermediates: a comparative study in vitro and ex vivo. Biochem Biophys Res Commun 164: 968-973 https://doi.org/10.1016/0006-291X(89)91764-6
  15. Bredt DS, Snyder SH. 1994. Nitric oxide: a physiologic 6 Sulkyoung Park et al. messenger molecule. Annu Rev Biochem 63: 175-195 https://doi.org/10.1146/annurev.bi.63.070194.001135
  16. Jang KH, Song KB, Kim CH, Chung BH, Kang SA, Chun UH, Choue RW, Rhee SK. 2001. Comparison of characteristics of levan produced by different preparations of levansucrase from Zymomonas mobilis. Biotechnol Lett 23: 339-344 https://doi.org/10.1023/A:1005641220946
  17. Mosmann T. 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J Immunol Methods 65: 55-63 https://doi.org/10.1016/0022-1759(83)90303-4
  18. Okimura T, Ogawa M, Yamauchi T. 1986. Stress and immune responses. III. Effect of resistant stress on delayed type hypersensitivity (DTH) response, natural killer (NK) activity and phagocytosis in mice. Jpn J Pharmacol 41: 229-235 https://doi.org/10.1254/jjp.41.229
  19. Ding AH, Nathan CF, Stuer DJ. 1988. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol 141: 2407-2412
  20. Leibovici J, Susskind-Brudner G, Wolman M. 1980. Direct antitumor effect of high-molecular-weight levan on Lewis lung carcinoma cells in mice. J Natl Cancer Inst 65: 391-396
  21. Stark Y, Leibovici J. 1986. Different effects of the polysaccharide levan on the oncogenicity of cells of two variants of Lewis lung carcinoma. Br J Exp Pathol 67: 141-147
  22. Calazans GMT, Lima RC, de Franca FP, Lopes CE. 2000. Molecular weight and antitumour activity of Zymomonas mobilis levans. Int J Biol Macromol 27: 245-247 https://doi.org/10.1016/S0141-8130(00)00125-2
  23. Yoo SH, Yoon EJ, Cha J, Lee HG. 2004. Antitumor activity of levan polysaccharides from selected microorganisms. Int J Biol Macromol 34: 37-41 https://doi.org/10.1016/j.ijbiomac.2004.01.002