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The Korean Association of Immunobiologists (대한면역학회)
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Comparison between Immunostimulatory Activity and Molecular Structure of Different Polysaccharides

인삼다당체 진산과 유사구조 다당체의 면역증강활성작용

  • Shim, Ji-young (Laboratory of Immunology, Korea Institute of Radiological and Medical Sciences, Laboratory of Biopharmaceutical Processes, Graduate School of Life Sciences and Biotechnology, Korea University) ;
  • Jung, In-Sung (Laboratory of Immunology, Korea Institute of Radiological and Medical Sciences) ;
  • Kim, Chan-Wha (Laboratory of Biopharmaceutical Processes, Graduate School of Life Sciences and Biotechnology, Korea University) ;
  • Yun, Yeon-Sook (Laboratory of Immunology, Korea Institute of Radiological and Medical Sciences) ;
  • Song, Jie-Young (Laboratory of Immunology, Korea Institute of Radiological and Medical Sciences)
  • 심지영 (원자력의학원 면역학연구실, 고려대학교 생명공학과) ;
  • 정인성 (원자력의학원 면역학연구실) ;
  • 김찬화 (고려대학교 생명공학과) ;
  • 윤연숙 (원자력의학원 면역학연구실) ;
  • 송지영 (원자력의학원 면역학연구실)
  • Published : 2004.06.30
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Abstract

Background: We previously reported that ginsan, a polysaccharide extracted from Panax ginseng had an immunostimulatory activity such as mitogenic activity, activation of macrophages and killer cells, and production of a variety of cytokines which resulted in antitumor and antiseptic effects. We further purified $\alpha$-(1$\longrightarrow$6)-glucan and $\beta$-(2$\longrightarrow$6)-fructan from the ginsan with size exclusion and ion-exchange column chromatography successively. In this study, we performed the structure-based activity of ginsan by comparison with known polysacchrides such as $\beta$-glucan, curdlan, laminarin, levan, dextran, lentinan and OK-432. Methods: To investigate the immunostimulatory activity of several polysaccharide compounds, we investigated the stimulation of lymphocytes proliferation, the generation of activated killer cells and the secretion of nitrites from activated macrophages. Results: Of polysaccharides tested, curdlan and ginsan stimulated lymphocyte proliferation, suggesting that the molecular weight and composition of polysaccharide are dependent on the mitogenic activity. The production of nitric oxide was significantly increased in curdlan, levan, ginsan and its fraction, indicating that fructan has also capacity to activate macrophages and may devote to kill pathogens. In addition, the activation of macrophages was seemed to be independent of molecular weight of polysaccharide. The generation of AK cells was exhibited in order of curdlan, OK-432> F1, ginsan, F3> levan> etc. The AK activity may be dependent on molecular weight and composition of polysaccharides. Conclusion: Unfortunately, purified polysaccharide from ginsan were less active on immunostimulatory activity than mixed compounds of polysaccharides. From the viewpoint of structure and activity relationships, we found several characteristic features.

Keywords

References

  1. Wimer BM: The ideal biological response modifier. Mol Biotherapy 1;311-317, 1989
  2. Talmadge JE, Herbermann RB: The preclinical screening laboratory: Evaluation of immunomodulatory and therapeutic properties of biological response modifiers. Cancer Treat Reports 70;171-182, 1986
  3. Terry WD, Rosenberg SA: Immunotherapy of Human Cancer. Elsevier North-Holland. New York, 1982
  4. Herbermann RB: Biological response modifiers for the treatment of cancer. In: Tsubura E, Urashizaki I, Aoki T, Sone S, Kaneto Y eds: Rationale of Biological response Modifiers in Cancer Treatment, p240-255, Excepta Medica, Princeton, 1985
  5. Talmadge JE, Herberman RB: The preclinical screening laboratory: Evaluation of immunomodulatory and therapeutic properties of biological response modifiers. Cancer Treat Rep 70;171-182, 1986
  6. Song JY, Han SK, Son EH, Pyo SN, Yun YS, Yi SY: Induction of secretory and tumoricidal activities in peritoneal macrophages by ginsan. Int Immunopharmacol 2;857-865, 2002 https://doi.org/10.1016/S1567-5769(01)00211-9
  7. Lee YS, Jung IS, Lee IR, Kim KW, Hong WS, Yun YS:Activation of multiple effector pathways of immune system by the antineoplastic immunomodulator acidic polysaccharide Ginsan isolated from Panax ginseng. Anticancer Res 17;323-332, 1997
  8. Riggi SJ, DiLuzio NR: Identification of a reticuloendothelial stimulating agent in zymosan. Am J Physiol 200;297-300, 1961
  9. Bacon JSD, Farmer VC, Jones D, Taylor IF: The glucan component of the cell wall of Baker's yeast (Saccharomyces cerevisiae) considered in relation to its ultra- structure. Biochem J 114;556-557, 1969
  10. Phaff HJ: Cell wall of yeasts. Annu Rev Microbiol 17;15-30, 1963 https://doi.org/10.1146/annurev.mi.17.100163.000311
  11. Zakany M, Chihara G, Fachet J: Effect of lentinan on tumor growth in murine allogeneic and syngeneic hosts. Int J Cancer 25;371-376, 1980 https://doi.org/10.1002/ijc.2910250311
  12. Singh PP, Whistler RL, Tokuzen R, Nakahara W: Scleroglucan, an antitumor polysaccharide from Sclerotium glucanicum. Carbohy Res 37;245-247, 1974 https://doi.org/10.1016/S0008-6215(00)87078-0
  13. DiLuzio NR, Williams DL, McNamee RB, Edwards BF, Kitahama A: Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan. Int J Cancer 24;773-779, 1979 https://doi.org/10.1002/ijc.2910240613
  14. Reynolds JA, Kastello MD, Harrington DG, Crabbs CL, Peters CJ, Jemski JV, Scott GH, DiLuzio NR: Glucan-induced enhancem ent of host resistance to selected infectious diseases. Infect Immun 30;51-57, 1980
  15. Tateishi T, Ohno N, Adahi Y, Yadomae T: Increases in Hematopoietic Responses Caused By $\beta$-Glucans in Mice. Biosci Biotech Biochem 61;1548-1553, 1997 https://doi.org/10.1271/bbb.61.1548
  16. Browder W, Williams DL, Lucore P, Pretus H, Jones E, McNamee RB: Effect of enhanced macrophage function on early wound healing. Surgery 104;224-230, 1988
  17. Ohno N, Asada N, Adachi Y, Yodomae Y: Enhancement of LPS triggered TNF-alpha (tumor necrosis factor-alpha) production by (1\longrightarrow3)-beta-D-glucans in mice. Biol Pharm Bull 18;126-133, 1995 https://doi.org/10.1248/bpb.18.126
  18. Ohno N, Miura N, Chiba N, Adachi Y, Yadomae T: Comparison of the immunopharmacological activities of triple and singlehelical schizophyllan in mice. Biol Pharm Bull 18;1242-1247, 1995 https://doi.org/10.1248/bpb.18.1242
  19. Kishida E, Kinoshita C, Sone Y, Misaki A: Structures and antitumor activities of polysaccharides isolated from mycelium of Volvariella volvacea. Biosci Biotechnol Biochem 56;1308-1309, 1992 https://doi.org/10.1271/bbb.56.1308
  20. Saito H, Yoshioka Y, Uehara N, Aketagawa J, Tanaka S, Shibata Y: Relationship between conformation and biological response for (1\longrightarrow3)-beta-D-glucans in the activation of coagulation factor G from limulus am ebocyte lysate and host-mediated antitumor activity. Demonstration of single-helix conformation as a stimulant. Carbohydr Res 217;181-190, 1991 https://doi.org/10.1016/0008-6215(91)84128-2
  21. Gomaa K, Kraus J, Franz G, Roper H: Structural investigations of glucans from cultures of Glomerella cingulata Spaulding & von Schrenck. Carbohydr Res 217;153-161, 1991 https://doi.org/10.1016/0008-6215(91)84125-X
  22. Demleitner S, Kraus J, Franz G: Synthesis and antitumour activity of derivatives of curdlan and lichenan branched at C-6. Carbohydr Res 226;239-246, 1992 https://doi.org/10.1016/0008-6215(92)84071-Y
  23. Tateishi T, Ohno N, Adachi Y, Yadomae, T: Increases in hematopoietic responses caused by beta-glucans in mice. Biosci Biotech Biochem 61;1548-1553, 1997 https://doi.org/10.1271/bbb.61.1548
  24. Tsuzuki A, Tateishi T, Ohno N, Adachi Y, Yadomae T: Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1\longrightarrow3)-beta-D-glucan preparation, Sonifilan, in cyclophospham ide-induced leukopenic mice. Biosci Biotech Biochem 63;104-110, 1999 https://doi.org/10.1271/bbb.63.104
  25. Ohno N, Hashimoto T, Adachi Y, Yadomae T: Conformation dependency of nitric oxide synthesis of murine peritoneal macrophages by beta-glucans in vitro. Immunology Letters 52;1-7, 1996 https://doi.org/10.1016/0165-2478(96)02538-2
  26. Harada T: Studies on bacterial gel forming $\beta$-1,3-glucans (Curdlan type polysaccharides) in Japan Proc IV IFS Ferment. Technol Today 603-607, 1972
  27. Ohna N, Kurachi K, Yadomae T: Physicochemical properties and antitumor activities of carboxymethylated derivatives of glucan from Sclerotinia sclerotiorum. Chem Pharm Bull 36;1016-1025, 1988 https://doi.org/10.1248/cpb.36.1016
  28. Sasaki T, Abiko N, Nitta K, Takasuka N, Sugino Y: Antitumor activity of carboxymethylglucans obtained by carboxymethylation of (1{\longrightarrow}3)-$\beta$-D-glucan from Alcaligenes faecalis var. myxogenes IFO 13140. Eur J Cancer 15;211-215, 1979 https://doi.org/10.1016/0014-2964(79)90062-8
  29. Williams DL, McNamee RB, Jones EL, Pretus HA, Ensley HE, Browder IW, Di Luzio NR: A method for the solubilization of $\alpha$(1{\longrightarrow}3)-$\beta$-D-glucan isolated from Saccharomyces cerevisiae. Carbohydr Res 219;203-213, 1991 https://doi.org/10.1016/0008-6215(91)89052-H
  30. Han YW: Microbial levan. Adv Appl Microbiol 35;171-194, 1990 https://doi.org/10.1016/S0065-2164(08)70244-2
  31. Kojima IT, Saito M, Iizuka N, Minamiura, Ono S: Characterization of levan produced by Serratia sp. J Ferment Bioeng 75;9-12, 1993 https://doi.org/10.1016/0922-338X(93)90169-9
  32. Chihara G : Recent progress in immunopharmacology and therapeutic effects of polysaccharides. Dev Biol Stand 77;19-197, 1992
  33. Okamoto H, Shoin S, Koshimura S, Shimizu R: Studies on the anticancer and streptolysin S-forming abilities of hemolytic streptococci. Jpn J Microbiol 11;323-336, 1967 https://doi.org/10.1111/j.1348-0421.1967.tb00350.x
  34. Oshimi K, Kano S, Takaku F, Okumura K: Augmentation of mouse natural killer cell activity by a streptococcal preparation, OK-432. J Natl Cancer Inst 65;1265-1269, 1980
  35. Saito M, Ebina T, Koi M, Yamaguchi T, Kamade Y, Ishida N:Induction of interferon-$\gamma$ in mouse spleen cells by OK-432, a preparation of Streptococcus pyogenes. Cell Immunol 68;187-192, 1982 https://doi.org/10.1016/0008-8749(82)90102-2
  36. Ichimura O, Suzuki S, Saito M, Sugawara Y, Ishida N:Augmentation of interleukin 1 and interleukin 2 production by OK-432. Int J Immunopharmacol 7;263-270, 1985 https://doi.org/10.1016/0192-0561(85)90035-9
  37. Fukui H, Koshihara Y, Nagamuta M, Mizutani Y, Uchida A:Production of interleukin 6 by human spleen cells stimulated with streptococcal preparation OK-432. Immunol Lett 21;127-130, 1989 https://doi.org/10.1016/0165-2478(89)90048-5
  38. Misaki T, Watanabe Y, Iida Y, Hidaka A, Kasagi K, Fukushima H, Konishi J: Recruitment of T lymphocytes and induction of tumor necrosis factor in thyroid cancer by a local immunotherapy. Cancer Immunol Immunother 35;92-96, 1992 https://doi.org/10.1007/BF01741855