Abstract
The high-sulfate-containing exopolysaccharide p-KG03 is produced by the red-tide microalga Gyrodinium impudicum strain KG03. The immunostimulatory effects of this sulfated exopolysaccharide were investigated by isolating peritoneal macrophages from mice 10 or 20 days after they had received a single dose of p-KG03 (100 or 200 mg/kg body weight). The cytotoxicity of the isolated macrophages for B16 tumor cells was tested, as B16 tumor cells are sensitive to tumor necrosis factor α (TNF-α) and nitric oxide. The activities of natural killer cells from the p-KG03-treated mice against YAC-1 mouse lymphoma cells were also tested. The nonspecific immune functions mediated by natural killer cells and macrophages were increased by treatment with p-KG03 in vivo. These results suggest that p-KG03 has immunostimulatory effects and enhances the tumoricidal activities of macrophages and NK cells in vivo. In addition, p-KG03 treatment increased the plaque-forming cell response to sheep red blood cells, as well as the levels of IgM and IgG Exposure to p-KG03 also increased the production by macrophages of cytokines, such as interleukins -1β and -6, and TNF-α. This is the first report of a marine microalgal sulfated polysaccharide having immunostimulatory activities. The p-KG03 polysaccharide may be useful for the development of biotechnological and pharmaceutical products that incorporate bioactive marine exopolysaccharides.
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References
DO Adams TA Hamilton (1984) ArticleTitleThe cell biology of macrophage activation Annu Rev Immunol 2 283–318 Occurrence Handle10.1146/annurev.iy.02.040184.001435 Occurrence Handle6100475
D Batinic FA Robey (1992) ArticleTitleThe V3 region of the enveloped glycoprotein of human immunodeficiency virus type 1 binds sulfated polysaccharides and CD4-derived synthetic peptides J Biol Chem 267 6664–6671 Occurrence Handle1551875
F Benencia MC Courreges FC Coulombie (2000) ArticleTitleIn vivo and in vitro immunomodulatory activities of Trichilia glabra aqueous leaf extracts J Ethnopharmacol 69 199–205 Occurrence Handle10.1016/S0378-8741(99)00010-0 Occurrence Handle10722201
N Bourgougnon M Lahaye C Chermann M Kornprobst (1993) ArticleTitleComposition and antiviral activities of a sulfated polysaccharide from Schizymenia Dubyi (Rodophyta, Gigatiales) bioorganic Med Chem Lett 3 1141–1146 Occurrence Handle10.1016/S0960-894X(00)80303-0
DS Bredt SH Snyder (1994) ArticleTitleNitric oxide: a physiologic messenger molecule Annu Rev Biochem 63 175–195 Occurrence Handle10.1146/annurev.bi.63.070194.001135 Occurrence Handle7526779
RA Burger AR Torres RP Warren VD Caldwell B Hughes (1997) ArticleTitleEchinacea-induced cytokine production by human macrophages Int J Immunopharmacol 19 371–379 Occurrence Handle10.1016/S0192-0561(97)00061-1 Occurrence Handle9568541
G Chihara (1984) ArticleTitleImmunopharmacology of lentinan and the glucans Rev Immunol Immunopharmacol 4 48–96
AH Ding CF Nathan DJ Stuehr (1998) ArticleTitleComparison of activating cytokines and evidence for independent production J Immunol 141 2407–2412
M Dubois KA Gilles JK Hamilton PA Rebers F Smith (1956) ArticleTitleColorimetric method for determination of sugars and related substances Anal Chem 38 350–356 Occurrence Handle10.1021/ac60111a017
PJ Duerksen-Hughes D Day SM Laster NA Zachariades L Aquino LR Gooding (1992) ArticleTitleBoth tumor necrosis factor and nitric oxide participate in lysis of simian virus 40–transformed cells by activated macrophages J Immunol 149 2114–2122 Occurrence Handle1325525
IJ Fidler (1985) ArticleTitleMacrophages and metastasis—a biological approach to cancer therapy: presidential address Cancer Res 4 4714–4726
DA Flick GE Gifford (1984) ArticleTitleComparison of in vitro cell cytotoxicity assays for tumor necrosis factor J Immunol 68 167–175
G Franz (1989) ArticleTitlePolysaccharide in pharmacy: current applications and future concepts Planta Medica 55 493–497 Occurrence Handle2694198
L Institoris O Siroki I Desi (1995) ArticleTitleImmunotoxicity study of repeated small doses of dimethoate and methylparathion administered to rats over three generations Hum Exp Toxicol 14 879–883 Occurrence Handle8588948
PP Jagodzinski M Lewandowska R Januchowski K Franciszkiewicz WH Trzeciak (2002) ArticleTitleThe effect of high molecular weight dextran sulfate on the production of interleukin-8 in monocyte cell culture Biomed Pharmacother 56 254–257 Occurrence Handle10.1016/S0753-3322(02)00198-1 Occurrence Handle12199625
A Jewett B Bonavida (1994) ArticleTitleActivation of the human immature natural killer cell subset by IL-12 and its regulation by endogenous TNF-alpha and IFM-gamma secretion Cell Immunol 154 273–286 Occurrence Handle10.1006/cimm.1994.1077 Occurrence Handle7907529
J Klostergaard (1985) ArticleTitleA rapid extremely sensitive, quantitative microassay for cytotoxic cytokines Lymphokine Res 4 309–317 Occurrence Handle3876491
LT Lebow B Bonavida (1990) ArticleTitlePurification and characterization of cytolytic and noncytolytic human natural killer cell subsets Proc Natl Acad Sci U S A 87 6063–6067 Occurrence Handle2143580
CJ Lowenstein EW Alley P Raval AM Snowman SH Snyder SW Russell WJ Murphy (1993) ArticleTitleMacrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide Proc Natl Acad Sci U S A 90 9730–9734 Occurrence Handle7692452
S McLellan M Jurd (1992) ArticleTitleAnticoagulants from marine algae Blood Coagul Fibrinolysis 3 69–77 Occurrence Handle1623121
M Mizuno Y Shiomi K Minato S Kawakami H Ashida H Tsuchida (2000) ArticleTitleFucogalactan isolated from Sarcodon aspratus elicits release of tumor necrosis factor-α and nitric oxide from murine macrophages Immunopharmacology 46 113–121 Occurrence Handle10.1016/S0162-3109(99)00163-0 Occurrence Handle10647870
CF Nathan RK Root (1977) ArticleTitleHydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering J Exp Med 146 1648–1662 Occurrence Handle10.1084/jem.146.6.1648 Occurrence Handle925614
M Otterle K Ostgaard G Skjak-Braek O Smidsrod P Soon-Shiong (1991) ArticleTitleInduction of cytokine production from human monocytes stimulated by alginate J Immunol 10 286–291
JG Park YS Park (1999) ArticleTitleComparison of morphological characteristics and the 24S rRNA sequences of Cochlodinium polykrikoides and Gyrodinium impudicum J Kor Soc Ocean 4 IssueID4 363–370
S Pyo JD Gangemi A Ghaffar EP Mayer (1991) ArticleTitlePolyI:C-induced anti-herpes simplex virus type I activity in inflammatory macrophages is mediated by induction of interferon-beta J Leukocyte Biol 50 479–487 Occurrence Handle1660913
LT Rasmussen R Selhelid (1989) ArticleTitleThe modulatory effect of lipoproteins on the release of interleukin 1 by human peritoneal macrophages sitmulated with β-1,3-D-polyglucose derivatives Scand J Immunol 29 477–484 Occurrence Handle2497512
I Saiki IJ Fidler (1984) ArticleTitleSynergistic activation of recombinant mouse interferon-γ and muramyl dipeptide of tumoricidal properties in mouse peritoneal macrophages J Immunol 135 684–688
DM See N Broumand L Sahl JG Tilles (1997) ArticleTitleIn vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients Immunopharmacology 35 229–235 Occurrence Handle10.1016/S0162-3109(96)00125-7 Occurrence Handle9043936
R Seljelid Y Figenschau J Bogwald LT Rasmussen R Aust-gulen (1989) ArticleTitleEvidence that tumor necrosis induced by aminated beta 1–3D polyglucose is mediated by a concerted action of local and systemic cytokines Scand J Immunol 30 687–694 Occurrence Handle2532395
KS Song SM Cho JH Lee HM Kim SB Han KS Ko ID Yoo (1995) ArticleTitleB-lymphocyte-stimulating polysaccharide from mushroom Phellinus linteus Chem Pharm Bull 43 2105–2108 Occurrence Handle8582012
DJ Stuehr MA Marletta (1985) ArticleTitleMammalian nitrate biosynthesis mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide Proc Natl Acad Sci U S A 82 7738–7742 Occurrence Handle3906650
H Sudo G Burgress H Takemasa N Nakamura T Matsunaga (1995) ArticleTitleSulfated exopolysaccharide production by the halophilic cyanobacterium Aphanocapsa halophyta Curr Microbiol 30 219–222 Occurrence Handle10.1007/BF00293636
IW Sutherland (1996) Extracellular polysaccharides. (1996) J Rechm G Reed A Puhler P Stadler (Eds) Biotechnology-VI VCH Weinhem Germany 615–657
K Takahashi Y Watanuki M Yamazaki S Abe (1988) ArticleTitleLocal induction of a cytotoxic factor in a murine tumor by systemic administration of an antitumor polysaccharide, MGA Br J Cancer 57 170–173 Occurrence Handle3358907
S Verstovsek D Maccubbin E Mihich (1992) ArticleTitleTumoricidal activation of murine resident peritoneal macrohage by interleukin 2 and tumor necrosis factor Cancer Res 52 3880–3885 Occurrence Handle1617664
Yim JH (2002). A Study on the Characterization and Production of Exopolysaccharide Produced by Marine Microalga Gyrodinium impudicum strain KG03. Ph.D. dissertation, University of Kyung-Hee, Seoul
JH Yim SJ Kim SH Ahn HK Lee (2003) ArticleTitleOptimal conditions for production of sulfated polysaccharide by marine microalga Gyrodinium impudicum strain KG03 Biomol Engineering 20 273–280 Occurrence Handle10.1016/S1389-0344(03)00070-4
JH Yim SJ Kim SH Ahn CK Lee KT Rhie HK Lee (2004) ArticleTitleAntiviral effects of sulfated exopolysacchride from the marine microalga Gyrodinium impudicum strain KG03 Mar Biotechnol 6 17–25 Occurrence Handle10.1007/s10126-003-0002-z Occurrence Handle14508657
Acknowledgments
This work was supported by grants to H.K.L. from the Development of Marine Novel Compounds Program of the Korean Ministry of Maritime Affairs and Fisheries and from the National Research Laboratory Program of the Korean Ministry of Science and Technology.
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Yim, J.H., Son, E., Pyo, S. et al. Novel sulfated polysaccharide derived from red-tide microalga Gyrodinium impudicum strain KG03 with immunostimulating activity in vivo. Mar Biotechnol 7, 331–338 (2005). https://doi.org/10.1007/s10126-004-0404-6
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DOI: https://doi.org/10.1007/s10126-004-0404-6