MGN-3/Biobran, modified arabinoxylan rice bran, has been shown to be a potent biological response modifier (BRM) as manifested by stimulation of different arms of the immune system such as NK, T and B cells; however, its effect on macrophages has not yet been studied. The effects of MGN-3 on macrophage function was examined in vitro using 3 models: human macrophage cell line U937, murine macrophage cell line RAW264.7, and murine peritoneal macrophages (P-Mφ). Treatment with MGN-3 resulted in an increase in the percentages of attachment and phagocytosis of yeast by macrophages. The effect depends on the type of macrophage and the dose of MGN-3 applied. Macrophages also demonstrated enhancement in their spreading ability, post treatment with MGN-3. Results also showed that MGN-3, in a dose-dependent manner (1, 10,100 μg/ml), significantly induced high levels of production of cytokines: TNF-α and IL-6. In addition, MGN-3 significantly increased nitric oxide (NO) production. This data demonstrates that MGN-3 is a potent inducer of phagocytic function by macrophage, and may suggest that MGN-3 is a useful agent for fighting microbial infection.
CavaillonJ.M.1994. Cytokines and macrophages. Biomed. Pharmacother.48:445.
2.
SongJ.Y.HanS.K.SonE.H.PyoS.N.YunY.S.YiS.Y., 2002. Induction of secretory and tumoricidal activities in peritoneal macrophages by ginsan. Int. Immunopharmacol.2:857
3.
FiliceG.A.1988. Antimicrobial properties of Kupffer cells. Infect. Immun.56:1430.
4.
Vazquez-TorresA.BalishE., 1997. Macrophages in resistance to candidiasis. Microbiol. Mol. Biol. Rev.61:170.
5.
DjaldettiM.SalmanH.BergmanM.DjaldettiR.BesslerH., 2002. Phagocytosis-the mighty weapon of the silent warriors. Microsc Res. Techn.15:421.
6.
PeppoloniS.ManciantiS.VolpiniG.NutiS.RuggieroP.RappuoliR.BlasiE.Del GiudiceG., 2002. Antibody-dependent macrophage-mediated activity against Helicobacter pylori in the absence of complement. Eur. J. Immunol.32:2721.
7.
AndradeR.M.WessendarpM.SubausteC.S., 2003. CD154 Activates Macrophage Antimicrobial Activity in the Absence of IFN-gamma through a TNF-alpha-Dependent Mechanism. J. Immunol.15:6750.
8.
CalandraT.2003. Macrophage migration inhibitory factor and host innate immune responses to microbes. Scand. J. Infect. Dis.35:573.
9.
SchreiberR.D.CeladaA., 1985. Molecular characterization of interferon-gamma as a macrophage activating factor. Lymphokines11:87.
10.
EunJ.S.SuhY.H.KimD.K.JeonH., 2000. Regulation of cytokine production by exogenous nitric oxide in murine splenocyte and peritoneal macrophage. Arch. Pharm. Res.23:531.
11.
ChapesS.K.HaskillS., 1983. Evidence for granulocyte-mediated macrophage activation after C. parvum immunization. Cell. Immunol.75:367.
12.
RaifordD.S.ThigpenM.C., Kupffer cell stimulation with Corynebacterium parvum reduces some cytochrome P450-dependent activities and diminishes acetaminophen and carbon tetrachloride-induced liver injury in the rat. Toxicol. Appl. Pharmacol.129:36.
13.
NeumannC.MacherE.SorgC., 1980. Interferon production by Corynebacterium parvum and BCG-activated murine spleen macrophages. Immunobiol. 157:12.
14.
GhoneumM.1998. Anti-HIV activity in vitro of MGN-3, an activated arabinoxylane from rice bran. Biochem. Biophys. Res. Commun.243:25.
15.
GhoneumM.1998. Enhancement of human natural killer cell activity by modified arabinoxylane from rice bran (MGN-3). Int. J. Immunother.14:89.
16.
GhoneumM.JewettA., 2000. Production of tumor necrosis factor- and interferon-from human peripheral blood lymphocytes by MGN-3, a modified arabinoxylan from rice bran, and its synergy with interleukin-2 in vitro. Cancer Detec. Prev.24:314.
17.
TazawaK.IchihashiK.FujiiT.OmuraK.AnazawaM.MaedaH., 2003. The orally administration of the hydrolysis rice bran prevents a common cold syndrome for the elderly people based on immunomodulatory function. J. Trad. Med.20:132.
18.
JacobyH.I.WnorowskiG.SakataK.MaedaH., 2001. The effect of MGN-3 on cisplatin and doxorubicin induced toxicity in the rat. J. Nutraceuticals Funct. Med. Foods3:3.
19.
EndoY.KanbayashiH., 2003. Modified rice Bran beneficial for weight loss of mice as a major and acute adverse effect of cisplatin. Pharmcol. Toxicol.92:300.
20.
GhoneumM.GollapudiS., 2003. Modified arabinoxylan rice bran (MGN-3/Biobran) sensitizes human T cell leukemia cells to death receptors (CD95)-induced apoptosis. Cancer Letter201:41.
21.
GhoneumM.GollapudiS., 2004. Modified arabinoxylan rice bran (MGN-3/Biobran) potentiates apoptosis in cancer cells induced by multiple anti-cancer agents in vitro. 7th International Symposium on Predictive Oncology & Intervention Strategies. February 7–10, Nice France, p. 1.
22.
PetrequinP. R.JohnsonA. G., 1984. Macrophage activation by adjuvants in aging mice. J. Leuko. Biol.35:251.
23.
GhoneumM.GrewalI.BrownJ.OsborneR.ElembabiH.GillG., 2003. Phagocytosis of Candida albicans by lymphatic tumour cells in vitro. Acta Histochem. 105:127.
24.
RuffM. R.GiffordG. E., 1980. Purification and physiological characterization of rabbit tumor necrosis factor. J. Immunol.125:1671.
25.
MatsudaT.HiranoT.KishimotoT., 1987. Establishment of an interleukin-6(IL-6)/B cell stimulatory factor 2-dependent cell line and preparation of anti-IL-6 monoclonal antibodies. Eur. J. Immunol.18:951.
26.
MosmanT.1983. Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxic assays. J. Immunol. Methods65:55.
27.
GreenL. C.WagnerD. A.GlogowskiJ.SkipperP. L.WishnokJ. S.TannenbaumS.R., 1982. Analysis of nitrate, nitrite, and [15N] nitrate in biological fluids. Anal. Biochem.126:131.
28.
GhoneumM.BrownJ., 1999. NK immunorestoration of cancer patients by MGN-3, a modified arabinoxylan rice bran (study of 32 patients followed for up to 4 years), In Anti-aging Medical Therapeutics. KlatzR.GoldmanR. ed. vol. III, Health Quest Publications Marina del Rey CA, p. 217.
29.
LimD. S.BaeK. G.JungI. S.KimC. H.YunY. S.SongJ. Y., 2002. Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation. J. Infect.45:32.
30.
JinR.WanL. L.MitsuishiT.SatoS.AkuzawaY.KodamaK.KurashigeS., 1994. Effect of shi-karon and Chinese herbs on cytokine production of macrophage in immunocompromised mice. Am. J. Chin. Med.22:255.
31.
KwonK. H.KimK. I.JunW. J.ShinD. H.ChoH. Y.HongB. S., 2002. In vitro and in vivo effects of macrophage-stimulatory polysaccharide from leaves of Perilla frutescens var. crispa. Bio. Pharm. Bull.25:367.
32.
HanS. B.ParkS. H.LeeK. H.LeeC. W.LeeS. H.KimH. C.KimY. S.LeeH. S.KimH. M., 2001. Polysaccharide isolated from the radix of Platycodon grandiflorum selectively activates B cells and macrophages but not T cells. Int. Immunopharmacol.1:1969.
33.
ChoiC.Y.KimJ. Y.KimY. S.ChungY. C.HahmK. S.JeongH. G., 2001. Augmentation of macrophage functions by an aqueous extract isolated from Platycodon grandiflorum. Cancer Lett. 166:17.
34.
RimbachG.ParkY.C.GuoQ.MoiniH.QureshiN.SaliouC.TakayamaK.VirgiliF.PackerL., 2000. Nitric oxide synthesis and TNF-alpha secretion in RAW 264.7 macrophages: Mode of action of a fermented papaya preparation. Life Sci. 67:679.
35.
AndradeR.M.WessendarpM.SubausteC.S., 2003. CD154 activates macrophage antimicrobial activity in the absence of IFN-gamma through a TNF-alpha-dependent mechanism. J. Immunol.171:6750.
VonkA.G.NeteaM. G.van KriekenJ.H.Van der MeerJ.W.KullbergB.J., 2002. Delayed clearance of intraabdominal abscesses caused by Candida albicans in tumor necrosis factor-alpha- and lymphotoxin-alpha-deficient mice. J. Infect. Dis.186:1815.
38.
MartinJ. H.EdwardsS.W., 1993. Changes in mechanisms of monocyte/macrophage-mediated cytotoxicity during culture. Reactive oxygen intermediates are involved in monocyte-mediated cytotoxicity, whereas reactive nitrogen intermediates are employed by macrophages in tumor cell killing. J. Immunol.150:3478.
39.
GorelikL.Bar-DaganY.MokyrM.B., 1996. Insight into the mechanism(s) through which TNF promotes the generation of T cell-mediated antitumor cytotoxicity by tumor bearer splenic cells. J. Immunol.156:4298.
40.
NaumeB.ShalabyR.LesslauerW.EspevikT., 1991. Involvement of the 55-and 75-kDa tumor necrosis factor receptors in the generation of lymphokine-activated killer cell activity and proliferation of natural killer cells. J. Immunol.146:3045.
41.
JewettA.BonavidaB., 1993. Pivotal role of endogenous TNF-alpha in the IL-2-dri ven activation and proliferation of the functionally immature NK free subset. Cell. Immunol.151:257.
42.
JewettA.BonavidaB., 1994. Pentoxifylline suppresses interleukin-2-mediated activation of immature human natural killer cells by inhibiting endogenous tumor necrosis factor-alpha secretion. J. Clinical. Immunol.14:31.
43.
JewettA.BonavidaB., 1994. Activation of the human immature natural killer cell subset by IL-12 and its regulation by endogenous TNF-alpha and IFN-gamma secretion. Cell. Immunol.154:273.
44.
GhoneumM.1995. Immunomodulatory and anticancer properties of MGN-3, a modified xylose from rice bran in 5 patients with breast cancer. Nov. 5–8 “Int. Conference Cancer, the interference between basic and applied research”, sponsored by the American Association for Cancer Res. Baltimore. MD, p.1.
45.
GhoneumM.NamatallaG., 1996. NK immunomodulatory function in 27 cancer patient by MGN-3, a modified arabinoxylane from rice bran. Abst., proceedings of the 87th Ann. Apr. 20–24. Meeting of American Assoc. for Cancer Res. Wash. DC, p. 1.
46.
OkadaM.KitaharaM.KishimotoS.MatsudaT.HiranoT.KishimotoT., 1988. IL-6/BSF-2 functions as a killer helper factor in the in vitro induction of cytotoxic T cells. J. Immunol.141:1543.
47.
HoussiauF.Van SnickJ., 1992. IL-6 and the T-cell response. Res. Immunol.143:740.
48.
LorsbachR. B.MurphyW.J.LowensteinC.J.SnyderS.H.RussellS.W., 1993. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. J. Biol. Chem.268:1908.
49.
PoliakovicM.KarpmanD.SvanborgC.PerssonK., 2002. Human renal epithelial cells express iNOS in response to cytokines but not bacteria. Kidney Int. 61:444.
50.
BogdanC.RollinghoffM.DiefenbachA., 2000. The role of nitric oxide in innate immunity. Immunol. Rev.173:17.
51.
ParkG.C.RyuJ. S.MinD. Y., 1997. The role of nitric oxide as an effector of macrophage-mediated cytotoxicity against Trichomonas vaginalis. Korean J. Parasitol.35:189.
52.
CifoneM.G.CironiL.MecciaM. A.RoncaioliP., 1995. Role of nitric oxide in cell-mediated tumor cytotoxicity. Adv. Neuroimmunol.5:443.
53.
PaulnockD.M.DemickK. P.CollerS. P., 2000. Analysis of interferon-gamma-dependent and -independent pathways of macrophage activation. J. Leukoc. Biol.67:677.
54.
Thoma-UszynskiS.StengerS.TakeuchiO.OchoaM. T., 2001. Induction of direct antimicrobial activity through mammalian toll-like receptors. Science23:291.
