巨噬細胞是具有高吞噬性功能的細胞，全身廣泛散佈，在宿主體內扮演著調控先天性免疫和發炎反應的重要角色。多醣體β-glucan為菇蕈類細胞壁上的主要成分之ㄧ，可活化體內多種免疫細胞、提高巨噬細胞吞噬能力，並促進細胞激素與干擾素的生成。本研究以體外試驗進行香菇菌絲多醣體對巨噬細胞活化及生理活性之探討。我們發現香菇菌絲多醣體刺激細胞增生測試中，發現隨著濃度作用增加，對細胞有增生之趨勢，且有增加一氧化氮產生量的效果，並顯著提升巨噬細胞吞噬能力及胞內ROS之提升。經由西方墨點法分析蛋白表現，iNOS表現量隨著香菇菌絲體作用濃度提高而上升，更進一步探討胞內轉錄蛋白機制，發現隨著香菇菌絲多醣體作用時間增加，IκB蛋白有磷酸化之現象，因而活化轉錄因子NFκB p65移轉至細胞核內。結果顯示香菇菌絲多醣體之活化巨噬細胞與NFκB路徑誘發iNOS之路經有關。

Macrophages are phagocytic cells widely distributed throughout the body, and play essential role in innate immunity and inflammatory responses. Polysaccharides β-glucan is the major component of mushroom cell walls which can activate immuno cells, increased phagocytic activity of macrophage, cytokine and interferon production. In this study, we attempt to investigate the biological activity of polysaccharide of Lentinus edodes mycelia (LEM) on activation of macrophage in vitro. We found that polysaccharide of LEM strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production and morphological changes. Western immunoblotting assays revealed that polysaccharide of LEM induced NO production of RAW264.7 macrophage through the increased expression of inducible nitric oxide synthase (iNOS), stimulated phosphorylation and degradation of IκB-α and subsequent NFκB p65 activation. Therefore, our data suggest that polysaccharide of LEM may promote macrophage activation via NFκB signaling pathways.

摘要 I
Abstract II
謝誌 IV
目錄 V
圖表目錄 VIII
第1章 前言 1
第2章 文獻回顧 4
2.1 香菇菌絲體（Lentinus edodes mycelia） 4
2.2 菇類之免疫生理活性 4
2.3 免疫反應 6
2.4 巨噬細胞（Macrophage） 6
2.5 多醣體β-glucan特性 7
2.6 多醣結構及活性之間的關係 9
2.7 β-glucan與免疫細胞的關係 10
2.8 一氧化氮（Nitric Oxide, NO） 11
2.9 一氧化氮的免疫反應 13
2.10 活性氧物質（Reactive oxygen species, ROS） 13
2.11 NFκB 15
2.12 一氧化氮合成酶（nitric oxide synthase, NOS）的表現 15
第3章 材料與方法 18
3.1 研究目的（Aim of experiment） 18
3.2 實驗架構 19
3.3 細胞株 (Cell line) 20
3.4 儀器設備 20
3.5 藥品試劑 20
3.5.1 樣品 20
3.5.2 抗體 21
3.5.3 常用藥品 21
3.6 樣品製備及初步結構分析 22
3.6.1樣品製備來源 22
3.6.2 多醣總醣含量測定 22
3.6.3 傅力葉紅外線光譜分析 23
3.7 細胞解凍 23
3.8 細胞繼代培養 23
3.9 細胞計數 23
3.10 細胞存活率分析（MTT assay） 23
3.11 Nitrite 測定與分析 24
3.12 蛋白質電泳與西方墨點法 25
3.12.1 蛋白質萃取 25
3.12.2 蛋白質定量 26
3.12.3 蛋白質電泳分析 27
3.12.4 轉印與免疫染色法 29
3.13 細胞內ROS產量之分析 31
3.14 老鼠巨噬細胞株RAW264.7吞噬作用之影響 31
3.15 老鼠巨噬細胞株RAW264.7吞噬螢光E.coli之觀察 32
3.16 免疫螢光分析（Immunofluorescence） 32
第4章 結果 33
4.1 香菇菌絲多醣體總醣量分析 33
4.2 傅力葉紅外線光譜（FTIR）分析 33
4.3 細胞存活率偵測分析（MTT assay） 33
4.4 巨噬細胞型態活化 34
4.5 Nitrite的測定與分析 34
4.6 香菇菌絲多醣體刺激RAW264.7吞噬作用之影響 35
4.7 ROS之測定 35
4.8 iNOS 酵素蛋白分析 36
4.9 香菇菌絲多醣體刺激RAW264.7細胞轉錄因子NFκB轉位偵測 37
4.10 IκBα蛋白質量分析 37
第5章 討論 55
第6章 結論 58
參考文獻 60
作者簡介 73

吳冠政。2006。 纖維素酶水解幾丁質聚糖及產生免疫活性評估。國立台灣海洋大學食品科學系研究所博士論文。
張毅偉。2003。 靈芝中具β-(1→6)分支之(1→3)-β-D-聚葡萄糖的性質與檢測。國立台灣大學食品科技研究所碩士論文。
曹巧吟。2003。 樟芝中免疫調節蛋白的純化與其生理活性之探討。國立台灣大學園藝學研究所碩士論文。
黎煥耀。2002。免疫系統。偉明圖書有限公司第1頁~第18頁。
王聖予，汪蕙蘭，楊志元，林志暉，劉定萍。2002 。免疫生物學。藝軒圖書出版社第2頁。
黃柏銘。2008。酵母β葡聚醣結構特性鑑定及活化巨噬細胞之探討。國立 屏東科技大學食品科學研究所碩士論文。
Althaus JS, Fici GJ, Plaisted SM, Kezdy FJ, Campbell CM, Hoogerheide JG and VonVoigtlander PF. 1997. Protein nitration by peroxynitrite : A method for monitoring nitric oxide neurotoxicity. Microchemical
Journal. 56: 155-64.
Blakeney AB, Harris PJ, Henry RJ and Stone BA. 1983. A simple and rapid preparation of alditol acetates for monosaccharide analysis.Carbohydrate Polymers 113: 291-9.
Baeuerle PA and Henkel T. 1994. Function and activation of NF-κB in the
immune system. Annual review of immunology 12: 141-79.
Baeuerle PA and Baltimore D. 1996. NF-κB: Ten Years After. Cell
87: 13-20.

Bogdan C. 2001. Nitric oxide and the immune response. Nature Immunologyy 2: 907-16.

Bohn JA and Bemiller JN. 1995. (1→3)-β-D-glucans biological response modifiers: a review of structure-functional activity relationships. Carbohydrate Polymers 28: 3-14.

Bredt DS, Hwang PM, Glatt CE, Lowenstein C, Reed RR and Snyder SH. 1991. Cloned and expressed nitric oxide synthase structurally resembles cytochrome P-450 reductase. Nature 351: 714-8.

Brown GD and Gordon S. 2003. Fungal beta-glucans and mammalian immunity. Immunity 19: 311-5.

Brown GD. 2006. Dectin-1: a signaling non-TLR pattern-recognition receptor. Nature Reviews 6: 33-43.

Cui S, Reichner JS, Mateo RB and Albina JE.（1994） Activated murine macrophages induce apoptosis in tumor cells through nitric oxide-dependent or –independent mechanisms. Cancer Research 54: 2462-7.
Castrillo A, Diaz-Guerra MJ, Hortelano S, Martin-Sanz P and Bosca L.
2000. Inhibition of IkappaB kinase and IkappaB phosphorylation by
15-deoxy-Delta(12,14)-prostaglandin J(2) in activated murine
macrophages. Molecular and Cellular Biology 20(5): 1692-98.
Chin F, Castranova V, Shi X and Demers LM. 1999. New insights into the
role of nuclear factor-kappa B, a ubiquitous transcription factor in the
initiation of disease. Clinical Chemistry 45: 7-17.

Cobb JP and Danner RL. 1996. Nitric oxide and septic shock. Journal of the American Medical Association Assoc. 275: 1192-96.
Deliconstantinos G, Villiotou V, Stavrides JC, Salemes N and Gogas J. 1995. Nitric oxide and peroxynitrite production by human erythrocytes: a causative factor of toxic anemia in breast cancer patients. Anticancer Research 15: 1435-46.

Garthwaite J. 1991. Glutamate, nitric oxide ane cell-cell signalling in the
nervous system. Trends in Neurosciences 14: 60-68.
Ghosh S, May MJ, and Kopp EB. 1998. NF-κB and Rel protrins: Evolutionarily conserved mediators of immune responses. Annual Review of Immunology 16: 225-60.

Graziewicz M, Wink DA and Laval F. 1996. Nitric oxide inhibit DNA ligase
activity: potential mechanisms for NO-mediated DNA damage.
Carcinogenesis 17:2501-05.
Green SJ, Nacy CA and Meltzer MS. 1991. Cytokine-induced synthesis of nitrogen oxides in macrophage: a protective host response to Leishmania and other intracellular pathogens. Journal of Leukocyte Biology 50: 93-103.

Gross SS and Wolin MS. 1995. Nitric oxide: pathophysiological mechanisms.
Annual Review of Physiology 57: 737-69.
Guha Mausumee and Mackman Nigel. 2001. LPS induction of gene expression in human monocytes. Cellular Signalling 13:85-94.
Gwinn MR. and Vallyathan V. 2006. Respiratory burst: role in signal transduction in alveolar macrophages. Journal of toxicology and environmental health. Part B, Critical Reviews 9(1): 27-39.
Hackett CJ. 2003. Innate immune activation as a broad-spectrum biodefense strategy: prospects and research challenges. The Journal of Allergy and Clinical Immunology 112: 686-94.
Hailman E, Vasselon T, Kelley M, Busse LA, Hu MC, Lichenstein HS, Detmers PA and Wright SD. 1996. Stimulation of macrophage and neutrophils by complexes of lipopolysccharide and soluble CD14.
Journal of Immunology 156: 4384-90.
Hanada T and Yoshimura A. 2002. Regulation of cytokine signaling and inflammation. Cytokine＆Growth Factor Review 13:413-21.
Hoebler C, Barry JL, David A and Delort-Laval J. 1989. Rapid acid hydrolysis of plant cell wall polysaccharides and simplified quantitative determination of their neutral monosaccharides by gas-liquid chromatography. Journal of Agricultural and Food Chemistry 37: 360-7

Janeway CA. 1989. Natural killer cells: a primitive immune system.
Nature 341,108.
Karpuzoglu E and Ahmed SA. 2006. Strogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, and apoptosis. Nitric Oxide 15: 177-86.
Karupiah G, Xie QW, Buller RM, Nathan C, Duarte C and MacMicking JD. 1993. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science 261: 1445-8.

Kataoka K, Muta T, Yamazaki S and Takeshige K. 2002. Ativation of macrophages by liner (1→3)-β-D-glucans. Impliations for the recognition of fungi by innate immunity. The Journal of Biological Chemistry 277: 36825-31.

Kim YT, Kim EH, Cheong C, Williams DL, Kim CW and Lim ST. 2000. Structure characterization of beta-D-（1→3, 1→6）-linked glucans using NMR spectroscopy. Carbohydrate Research 328: 331-41.

Kishida E, Sone Y and Misaki A. 1992. Effects of branch distribution and chemical modifications of antitumor (1→3)-β-D-glucans. Carbohydrate Research 17: 89-95.

Knowles RG and Moncada S. 1994. Nitric oxide synthases in mammals.
The Biochemical Journal 298: 249-58.
Kulicke WM, Lettau AI and Thielking H. 1997. Correlation between immunological activity, molar mass, and molecular structure of different (1→3)-beta-D-glucans. Carbohydrate Research 297: 135-43.

Lane TE, Otero GC, Wu-Hsieh BA and Howard DH. 1994. Expression of inducible nitric oxide synthase by stimulated macrophages correlates with their antihistoplasma activity. Infection and Immunity 62: 1478-9.

Larlux FS, Pavlick KP, Hines IN, Kawachi S, Harada H, Bharwani S, Hoffman JM and Grisham MB. 2001. Role of nitric oxide in
inflammation. Acta physiologica Scandinavica 173: 113-18.
Lawrence T. 2007. Inflammation and cancer: a failure of resolution. Trends in pharmacological sciences 28: 162-65.
Lechner M, Lirk P and Rieder J. 2005. Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin. Seminars in
Cancer Biology 15(4): 277-89.
Lee MH, Han DW, Baek HS, Lim HR, Lee IS, Lee KY, Kim KT, Lee SJ and Park JC. 2007. Differential cytokine responses of murine macrophage J774A.1 cells to stainless steel coated with and without hydroxyapatite.
Surface and Coatings Technology 201: 5729-32.
Leung MY, Liu C, Koon JC and Fung KP. 2006. Polysaccharide biological response modifiers. Immunology Letters 105: 101-14.

Lolis E and Bucala R. 2003. Therapeutic approaches to innate immunity: severe sepsis and septic shock. Nature Reviews 2: 635-45.

Khodr B and Khalil Z. 2001. Modulation of inflammation by reactive oxygen species: implications for aging and tissue repair. Free radical.
Biology & Medicine 30: 1-8.
Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E and Burmester GR. 2000. Macrophages in rheumatoid arthritis. Arthritis Research
2: 189-202.
Knowles RG and Moncada S. 1992. Nitric oxide as a signal in blood vessels. Trends in Biochemical Sciences 17: 39-42.

Lukhoba CW, Simmonds MS and Paton AJ. 2006. Plectranthus: a review of ethnobotanical uses. Journal of Ethnopharmacology 103(1): 1-24.
MacMicking JD, Nathan C and Hom G. 1995. Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase. Cell 81: 641-50.

Maeda YY and Chihara G. 1973. The effects of neonatal thymectomy on the antitumor activity of lentinan, carboxymethylpachymaran and zyosan, and their effects on various immune responses. International Journal of Cancer 11: 153-61.

Marletta MA. 1993. Nitric oxide synthase structure and mechanism. The
Journal of Biological Chemistry 268: 12231-4.
Matu EN and Van SJ. 2003. Antibacterial and anti-inflammatory activities of some plants used for medicinal purposes in Kenya. Journal of Ethnopharmacol 87(1): 35-41.
Mercurio F, Zhu H, Murray BW, Shevcheko A, Bennett BL, Li J, Young DB,
Barbosa M, Mann M, Manning A and Rao A. 1997. IKK-1 and IKK-2: cytokine-activated Ikappa B kinases essential for NF-kpappa B
activation. Science 278:860-66.
Moncada S, Palmer RM and Higgs EA. 1991.Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological
Reviews 43: 109-42.
Mori M and Gotoh T. 2000. Regulation of nitric oxide production by arginine metabolic enzymes. Biochemical and Biophysical Research
Communications 275: 715-9.
Misaki A, Kawaguchi K, Miyaji H, Nagae H, Hokkoku S, Kakuta M, Sasaki T. 1984. Structure of pestalotan, a highly branched（1→3）-beta-D-glucan elaborated by pestalotia sp. 815, and the enhancement of its antitumor activity by polyol modification of the side chains. Carbohydrate Research 129: 209-27.

Nathan C. 1992. Nitric oxide as a secretory product of mammalian cells. The FASEB Journal 6: 3051-64.

Nathan C and Xie QW. 1994. Regulation of biosynthesis of nitric oxide. The
Journal of Biological Chemistry 269: 13725-28.
Nishikawa M, Sato EF, Kuroki T, Utsumi K and Inoue M. 1998. Macrophage-derived nitric oxide induces apoptosis of rat hepatoma cells in vivo. Hepatology 28: 1474-64.

Nobunaga T, Tokugawa Y, Hasimoto K, Kubota Y Sawai K and Kimura T. 1996. Elevated nitric oxide concertration in plasma of inferile males: nitric oxide inhibit sperm motility. American journal of reproductive
Immunology 36: 193-7.
Nogare AR and Yarbrough WC Jr. 1990. A comparison of the effects of intact and deacylated lipopolysaccharide on human polymorphonuclear
leukocytes. The Journal of Immunology 144: 1404-10.
Nordberg J and Arnér ES. 2001. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free radical Biology & Medicine 31: 1287-312.
Nussler AK and Billiar TR. 1993. Inflammation, immunoregulation, and inducible nitric oxide synthase. Journal of Leukocyte Biology 54:171-8.
O’Neill GP and Ford-Hutchinson AW. 1993. Expession of mRNA for
cyclooxygenase-1 and cyclooxygenase-2 in human tissue. FEBS Lett.
330: 156-60.
Otterbein LE. 2002. Carbon monoxide: innovative anti-inflammatory properties of an age-old gas molecule. Antioxidants and Redox Signaling
4: 309-19.
Pae HO, Jeong GS, Kim HS, Woo WH, Rhew HY, Kim HS, Sohn DH, Kim YC and Chung HT. 2007. Costunolide inhibits production of tumor necrosis factor-alpha and interleukin-6 by inducing heme oxygenase-1 in
RAW264.7 macrophages. Inflammation Research 56: 520-26.
Palmer RM, Rees DD, Ashton DS and Moncada S. 1988. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochemical and Biophysical Research Communications 153: 1251-56.

Phipps RP, Stein SH and Roper RL. 1991. A new view of prostagandin E regulation of the immune response. Immunology Today 12: 349-52.
Quill H, Gaur A and Phipps RP. 1989. Prostaglandin E2-dependent induction of granulocyte-macrophage colony-stimulating factor secretion by coloned murine helper T cells. Journal of Immunology 142: 813-18.
Qureshi ST, Gros P and Malo D. 1999. The LPS locus: Genetic regulation of host respones to bacterial lipopolysaccharide. Inflammation Research
48: 613-20.
Radomski MW and Salas E. 1995. Nitric oxide-biological mediator, modulator and factor of injury: it is role in the pathogenesis of
atherosclerosis. Atherosclerosis 118: S69-80.
Rahman I, Biswas SK and Kode A. 2006. Oxidant and antioxidant balance in the airways and airway diseases. European Journal of Phamacology 533: 222-39.
Rees DD, Palmer RM and Moncada S. 1898. Role of endothelium-derived
nitric oxide in theregulation of blood pressure. Proceedings of the National Academy of Sciences of the United States of America
86: 3375-78.
Ritz J, Schmidt RE, Michon J, Hercend T and Schlossman SF. 1988. Characterization of functional surface structures on human natural killer
cells. Advances in Immunology 42: 181-211.
Robbins RA, Hadeli K, Nelson D, Sato E and Hoyt JC. 2000. Nitric oxide, peroxynitrite, and low respiratory tract inflammation.
Immunopharmacology 48: 217-21.
Rosselli M, Dubey RK, Imthurn B, Macas E and Keller PJ. 1995. Effect of nitric oxide on human spermatozoa: evidence that nitric oxide decreases sperm morility and induces sperm toxicity. Human Reprod
10: 1786-90.
Sakurai T, Ohno N, Yadomae T. 1996. Effect of fungal beta-glucan and interferon-gamma on the secretory function of murine alveolar macrophages. Journal of Leukocyte Biology 60: 118-24.

Salgo MG, Bermudez E, Squadrito GL and Pryor WA. 1995. DNA Damage and Oxidation of Thiols Peroxynitrite Causes in Rat
Thymocytes. Archives of Biochemistry and Biophysics 322(2): 500-05.
Sautebin L. 2000. Prostaglandins and nitric oxide as molecular target for
anti-inflammatory therapy. Fitoterapia 71: S48-57.
Schepetkin IA and Quinn MT. 2006. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential. International Immuno- pharmacology 6: 317-33.

Schwacha MG. 2003. Macrophages and post-burn immune dysfunction.
The Burn 29: 1-14.
Sen R and Baltimore D. 1986. Inducibility of kappa immunoglobulin enhancer-binding protein NF-kappa B by a posttranslational mechanism.
Cell 47: 921-28.
Silva D, Correia J, Soldau K, Christen U, Tobias PS and Ulevitch RJ. 2001. Liopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. The Journal of Biological Chemistry
276: 21129-35.
Siebenlist U, Franzoso G and Brown R. 1994. Structure, regulation and function of NF-κB. Annual Review of Cell Biology 10: 405-55.

Sprangers F, Sauerwein HP, Romijn JA, van Woerkom GM and Meijer AJ. 1998. Nitric oxide inhibits glycogen synthesis in isolated rat
hepatocytes. The Biochemical Journal 330: 1045-49.
Sporn MB and Robert AB. 1986. Peptide growth factors and inflammation, tissue repair, and cancer. The Journal of Clinical Investigation
78: 329-32.
Stamler JS, Single DJ and Loscalzo J. 1992. Biochemistry of nitric oxide and its redox-activited forms. Science 258: 1898-902.
Steinle JJ. 2007. Sympathetic neurotransmission modulates expression of inflammatory markers in the rat retina. Experimental Eye Research
84: 118-25.
Stokke BT, Elgsaeter A, Hara C, Kitamura S and Takeo K. 1993. Physicochemical properties of (1→6)-branched(1→3)-beta-D-glucans. 1. Physical dimensions estimated from hydrodynamic and electron microscopic data. Biopolymers 33: 561-73.

Storz peter. 2005. Reactive oxygen species in tumor progression. Frontiers in Biosctience 10: 1881-96.
Sveinbjφrnsson B, Olsen R, Seternes OM, Seljelid R. 1996. Macrophage cytotoxicity against murine meth A sarcoma involves nitric oxide-mediated apoptosis. Biochemical and Biophysical Reasearch Communications 223: 643-9.
Tabata Y and Ikada Y. 1988. Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials 9: 356-62.

Thompson JE, Phillips RJ, Erdjument-Bromage H, Tempst P and Ghosh S. 1995. IκB-β regulates the persistent response in a biphasic
activation of NF-κB. Cell 80: 573-82.
Ulevitch RJ and Tobias PS. 1999. Recognition of gram-negative bacteria and endotoxin by the innate immune system. Current Opinion in
Immunology 11: 19-22.
Uthaisangsook S, Day NK, Bahna SL, Good RA and Haraguchi S. 2002. Innate immunity and its role against infections. Annals of Allergy Asthma and Immunology 88: 253-64.

Velasco M, Diaz-Guerra MJ, Martin-Sanz P, Alvarez A and Bosca L. 1997. Rapid up regulation of IκBβ and abrogation of NF-κB activity in peritoneal macrophages stimulated with lipopolysaccharide.
The Journal of Biological Chemistry 272: 23025-30.
Verma IM, Stevenson JK, van AD and Miyamoto S. 1995. Rel/ NF-κB/IκB family: intimatetales of association and dissociation. Genes &
Development 9: 2723-35.
Vinegar R, Schreiber W and Hugo R. 1969. Biphasic development of carrageenan edema in rats. The Journal of Pharmacology and
Experimental Therapeutics 166: 96-103.
Vural C and Gungor A. 2003. Nitric oxide and the upper airways: recent discoveries. Journal of ear, nose, and throat 10(1): 39-44.
Ward C, Walker A, Dransfield I, Haslett C and Rossi AG. 2004. Regulation of granulocyte apoptosis by NF-kappaB. Biochemical Society Transactions 32: 465-7.

Williams DL, Pretus HA, McNamee RB, Jones EL, Pretus HA, Ensley HE, Browder IW and Di Luzio NR. 1991. A method for the solubilization of a (1→3)-beta-D-glucan isolated from saccharomyces cerevisiae. Carbohydrate Research 219: 203-13.

Xie QW, Cho H, Calaycay J, Mumford RA, Swiderek KM, LeeTD, Ding A, Troso T and Nathan C. 1992. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 256: 225-8.

Xie Qw, Cho H, Kashiwabara Y, Baum M, Weidner JR, Elliston K, Mumford R and Nathan C. 1994. Carboxyl terminus of inducible nitric oxide synthase: Contribution to NADPH binding and enzymatic activity. The Journal of Biological Chemistry 269: 28500-5.

Yao K, Iwashita A, Yao T, Takemura S, Furukawa K, Matsui T and Aoyagi K. 1996. Increased numbers of macrophages in noninflamed gastroduodenal mucosa of patients with Crohn's disease. Digestive Diseases and Sciences 41: 2260-67.

Yoshida T. 2001. Synthesis of polysaccharides having specific biological activiries. Progress in Polymer Science 26: 279-441.

Youdim MBH, Lavie L and Riederer P. 1994. Oxygen free radicals and neurodegeneration in Parkinson’s disease: a role for nitric oxide. Annals of the New York Academy of Sciences 738: 64-7.

Zimmerman JW, Lindermuth J, Fish PA, Palace GP, Stevenson TT and DeMong DE. 1998. A novel carbohydrate-glycosphingolipid interaction between a beta-(1-3)-glucan immunomodulator, PGG-glucan, and lactosylceramide of human leukocytes. The Journal of Biological Chemistry 273: 22014-20.