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研究生:廖詩芬
研究生(外文):Shih-Fen Liao
論文名稱:含岩藻糖的靈芝多醣體誘發抗腫瘤抗體之研究
論文名稱(外文):Immunization of Fucose-containing Polysaccharides from Reishi Mushroom Exerts Antibody-mediated Antitumor Activity
指導教授:翁啟惠翁啟惠引用關係
指導教授(外文):Chi-Huey Wong
口試委員:邱繼輝吳宗益林國儀
口試委員(外文):Kay-Hooi KhooChung-Yi WuKuo-I Lin
口試日期:2013-07-31
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:生化科學研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:英文
論文頁數:74
中文關鍵詞:Globo H抗體抗腫瘤靈芝多醣體
外文關鍵詞:Anti-Globo H antibodyAntitumorReishi Mushroom Polysaccharide
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靈芝在分類學上屬於擔子菌綱,為典型的(中)藥用真菌代表。針對多醣體之生物活性,過去的研究發現,病原性微生物(例如: Haemophilus influenza type B 和 Streptococcus pneumonia)的細胞壁多醣屬於免疫原,其抗原主要是結構主要是由特定寡糖單元重覆性排列所組成之高分子,臨床上此類抗原可引起T細胞非依賴型之抗體免疫反應。自古以來,靈芝常被當作免疫調節的保健品或抗癌的輔助品,儘管。有效成分與抗癌的機轉仍在持續研究當中,我們推測靈芝所富含的多醣體成分與活化人體免疫能力之功效有關。從醣類生物學的角度,醣鏈末端具有岩藻糖或唾液酸修飾屬於重要的腫瘤相關醣類抗原之醣化特徵,根據生物表面獨特的醣類結構作為抗原標靶,發展以碳水化合物為基礎的醣類接合型疫苗,已證實可有效的治療癌症與感染症。本研究為探討含岩藻糖的靈芝多醣體是否具有活化抗體生成協同抗腫瘤作用,我們將靈芝多醣體萃取物 (命名為F3 and F3 subfraction, FMS) 採取腹腔注射法免疫小鼠,在移植鼠源性肺腺癌細胞(LLC1)誘發小鼠原位腫瘤的動物模式中,活體試驗結果顯示,受免疫的腫瘤小鼠可延緩癌細胞的生長與降低癌症相關的發炎物質分泌;在探討抗腫瘤的機制中,我們首先發現受免疫的健康小鼠之免疫血清(in vitro)具毒殺癌細胞的活性,進一步利用全醣晶片高通量篩檢抗體的特異性,證實免疫血清中IgM抗體所辨識之醣分子與腫瘤醣類抗原相關,其抗原決定基最小單元是Fuca1-2Gab1-3GalNAc-R;例如:著名的六分子醣脂質Globo H (Fucα1-2Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ),已知大量表現於乳癌、乳癌幹細胞、肺癌、卵巢癌等多種癌細胞組織中。儘管採用腹腔注射多醣體,活化小鼠體內的免疫系統之運作機制尚未通盤釐清,有趣的是我們發現受免疫的健康小鼠腹腔內的B1 B-細胞數目顯著增加,在體外(in vitro)實驗中,我們更進一步證明靈芝多醣體可刺激受免疫小鼠的B1 B-細胞之分化與抗體分泌,種種證據符合過去的研究報導推測,此亞型B-細胞的活化與其所特有辨識多醣分子之能力有關。本研究中我們除了證明免疫血清的抗腫瘤活性與癌細胞表面Globo H醣類抗原的表現有關,更進一步,我們證實了靈芝多醣體的岩藻糖修飾會直接影響小鼠抗腫瘤抗體的生成,因此,在醣類結構的鑑定上,我們首先著眼於醣鏈末端具岩藻糖的鍵結方式與醣鏈定序。配合使用岩藻糖水解酵素、化學性酸水解與化學衍生化的方式調理靈芝多醣體 (FMS),綜合各式質譜儀測定的結果,我們推測其主幹由1,4連結的甘露聚糖和1,6連結的半乳聚糖兩種多醣聚合物構成,其末端含岩藻糖的鍵結特徵為Fucα1-2Gal,Fucα1-3/4Man,Fucα1-4Xyl 和 Fucα1-2Fuc;因此,我們預期此分析結果所提供的醣鏈資訊,將有利於爾後含岩藻醣的靈芝多醣體之結構鑑定。總結,本研究提出一可行的天然物多醣體之活性篩選模式,不僅突顯全醣晶片的應用價值,我們也闡述了靈芝多醣體誘發特異性抗醣類抗體具抗腫瘤的免疫機制。

Ganoderma lucidum (Reishi), a mushroom commonly used as a Chinese herb medicine, contains complex polysaccharides that have been used as an antitumor supplement with a rarely understood mechanism of immune response. Here we demonstrated that the mice immunized with a fucose-enriched Reishi polysaccharide fraction (designated as FMS) were able to induce antibodies against murine Lewis lung carcinoma (LLC1) cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular monocyte chemoattractant protein-1, MCP-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycan antigens, with the antigenic structure located in the non-reducing termini, i.e., Fuca1-2Galb1-3GalNAc-R(where R represents reducing end), typically found in Globo H and related tumor antigens. Although the composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-a-galactan, a fucose-dependent nanoLC-tandem MS analysis uncovered the Fuca1-2Gal, Fuca1-3/4Man, Fuca1-4Xyl and Fuca1-2Fuc linkages in the non-reducing termini of the FMS glycans, underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycan antigens. In summary, our development of carbohydrate immunomodulation-based therapy, which successfully correlated the high-throughput glycan microarray analysis with detailed structural analyses of glycan antigens, should be applicable to other medicinal polysaccharides.

1.Introduction(1)
1.1 Basidiomycetes polysaccharide(1)
1.2 Polysaccharide-based vaccine(3)
1.3 Carbohydrate mimicry and autoantibody induction(8)
1.4 Specific aims(12)
2. Methods and Materials(15)
2.1 Purification of a fucose-enriched F3 polysaccharides fraction, FMS(16)
2.2 Characterization of FMS(16)
2.3 Glycan binding analysis of serum IgM antibodies(17)
2.4 Hydrolysis reaction(18)
2.5 Fucose-based nanoLC-tandem MS analysis(19)
2.6 Mice immunization schedule and the lung tumor model(20)
2.7 Serological analysis of serum antibodies(21)
2.8 Fucose-specific plant lectins binding(22)
2.9 Cell cultures and FACS analysis(23)
2.10 Mouse cytokine/chemokine detection(24)
2.11 Antibody-mediated complement-dependent cytotoxicity (CDC) analysis(24)
2.12 Binding competition assay(25)
3. Results and Discussions(26)
3.1 Antitumor activity of F3(26)
3.2 Characterization of fucose-enriched polysaccharides,FMS (28)
3.3 The glycan-binding specificity of the sera IgM antibodies obtained from FMS- treated mice(30)
3.4 FMS possesses antitumor efficacy in vivo(32)
3.5 Terminal fucose of FMS is important for the antibody-mediated antitumor efficacy(33)
3.6 Immunization of FMS stimulates B1 B-cell activation(37)
3.7 Identification of fucosyl glycan moieties of FMS by MS-based approach(39)
3.8 Summary(41)
4. Figures(43)
1.1 Experimental design(13)
4.1 Antitumor effects of F3(43)
4.2 Glycan microarray analysis of F3-treated mice sera(45)
4.3 List of 60 synthetic glycan structures of the fabricated glycan chips(46)
4.4 Representative MALLS profiles of polysaccharides from our Reishi extract(47)
4.5 Glycan-binding patterns of the serum IgM antibodies as measured by the CFG glycan microarray(48)
4.6 A spectrum of tumor associated-glycans highly recognized by FMS-induced sera(49)
4.7 Antitumor activities of fucose-enriched F3 polysaccharides, FMS(50)
4.8 Terminal fucose of FMS is important for the antibody-mediated antitumor efficacy(52)
4.9 Terminal fucose of FMS is correlated with specific antiglycan IgM production(54)
4.10 B1 B-cell expansion in the mice immunization with our Reishi polysaccharides, FMS(55)
4.11 (A)Competition assay;(B)MALDI-MS mapping(57)
4.12 Targeted nanoLC-MS/MS glycan sequencing(58)
4.13 Fucosylated epitope linkage determination of permethylated FMS hydrolysate alditols(59)
4.14 Possible structures of FMS(60)
4.15 Fucose-containing Reishi polysaccharides exert antibody-mediated antitumor activity(45)
5.Tables(62)
1.1 Antitumor mushroom polysaccharides(15)
1.2 Examples of streptococcal capsular polysaccharides by exiting or Developmental carbohydrate-based vaccines(15)
5.1 Glycosyl-linkage composition of FMS and DFMS(62)
5.2 List of glycans bound by F3-induced sera IgM as ranked in decreasing order of binding intensities(63)
5.3 Compositional assignments of multiple charged sodiated molecular ions Observed in nanoLC-MS spectra of permethylated FMS hydrolysate alditols(67)
6.References(68)



1.Ooi VE & Liu F (2000) Immunomodulation and anti-cancer activity of polysaccharide-protein complexes. Curr Med Chem 7:715-729.
2.Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60:258-274.
3.Ren L, et al. (2012) Antitumor activity of mushroom polysaccharides: a review. Food Funct 3:1118-1130.
4.Lin ZB & Zhang HN (2004) Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms. Acta Pharmacol Sin 25:1387-1395.
5.Wasser SP & Weis AL (1999) Therapeutic effects of substances occurring in higher Basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65-96.
6.Thornton BP, et al. (1996) Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J Immunol 156(3):1235-1246.
7.Brown GD, et al. (2002) Dectin-1 is a major beta-glucan receptor on macrophages. J Exp Med 196:407-412.
8.de Jong MA, et al. (2010) C-type lectin Langerin is a beta-glucan receptor on human Langerhans cells that recognizes opportunistic and pathogenic fungi. Mol Immunol 47:1216-1225.
9.Bittencourt VC, et al. (2006) An alpha-glucan of Pseudallescheria boydii is involved in fungal phagocytosis and Toll-like receptor activation. J Biol Chem 281:22614-22623.
10.Luther K, et al. (2007) Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2. Cell Microbiol 9:368-381.
11.Wang YY, et al. (2002) Studies on the immuno-modulating and antitumor activities of Ganoderma lucidum (Reishi) polysaccharides: functional and proteomic analyses of a fucose-containing glycoprotein fraction responsible for the activities. Bioorg Med Chem 10:1057-1062.
12.Lin KI, et al. (2006) Reishi polysaccharides induce immunoglobulin production through the TLR4/TLR2-mediated induction of transcription factor Blimp-1. J Biol Chem 281:24111-24123.
13.Chen WY, et al. (2010) Effect of Reishi polysaccharides on human stem/progenitor cells. Bioorg Med Chem 18:8583-8591.
14.Hsu TL, et al. (2009) Profiling carbohydrate-receptor interaction with recombinant innate immunity receptor-Fc fusion proteins. J Biol Chem 284:34479-34489.
15.Josefsberg JO & Buckland B (2012) Vaccine process technology. Biotechnol Bioeng 109:1443-1460.
16.Heidelberger M & Avery OT (1923) The Soluble Specific Substance of Pneumococcus. J Exp Med 38:73-79.
17.Mac LC & Hodges RG (1945) Prevention of pneumococcal pneumonia by immunization with specific capsular polysaccharides. J Exp Med 82:445-465.
18.Austrian R & Gold J (1964) Pneumococcal Bacteremia with Especial Reference to Bacteremic Pneumococcal Pneumonia. Ann Intern Med 60:759-776.
19.Musher DM (1992) Infections caused by Streptococcus pneumoniae: clinical spectrum, pathogenesis, immunity, and treatment. Clin Infect Dis 14:801-807.
20.Sorensen UB, et al. (1990) Covalent linkage between the capsular polysaccharide and the cell wall peptidoglycan of Streptococcus pneumoniae revealed by immunochemical methods. Microb Pathog 8:325-334.
21.Astronomo RD & Burton DR (2010) Carbohydrate vaccines: developing sweet solutions to sticky situations? Nat Rev Drug Discov 9:308-324.
22.Abeygunawardana C, et al. (1989) The complete structure of the capsular polysaccharide from Streptococcus sanguis 34. Carbohydr Res 191:279-293.
23.Abeygunawardana C, et al. (1990) Complete structure of the polysaccharide from Streptococcus sanguis J22. Biochemistry 29:234-248.
24.Reddy GP, et al. (1993) Determination by heteronuclear NMR spectroscopy of the complete structure of the cell wall polysaccharide of Streptococcus sanguis strain K103. Anal Chem 65:913-921.
25.van Dam JE, et al. (1990) Immunogenicity and immunochemistry of Streptococcus pneumoniae capsular polysaccharides. Antonie Van Leeuwenhoek 58:1-47.
26.Goebel WF (1939) Studies on Antibacterial Immunity Induced by Artificial Antigens : I. Immunity to Experimental Pneumococcal Infection with an Antigen Containing Cellobiuronic Acid. J Exp Med 69:353-364.
27.Smit P, et al. (1977) Protective efficacy of pneumococcal polysaccharide vaccines. JAMA 238:2613-2616.
28.Bentley SD, et al. (2006) Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet 2:e31.
29.Yother J (2011) Capsules of Streptococcus pneumoniae and other bacteria: paradigms for polysaccharide biosynthesis and regulation. Annu Rev Microbiol 65:563-581.
30.Makela PH (1984) Capsular polysaccharide vaccines today. Infection 12 Suppl 1:S72-77.
31.Bardotti A, et al. (2005) Size determination of bacterial capsular oligosaccharides used to prepare conjugate vaccines against Neisseria meningitidis groups Y and W135. Vaccine 23:1887-1899.
32.Robbins JB, et al. (1983) Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups. J Infect Dis 148:1136-1159.
33.Johnson SE, et al. (1999) Correlation of opsonophagocytosis and passive protection assays using human anticapsular antibodies in an infant mouse model of bacteremia for Streptococcus pneumoniae. J Infect Dis 180:133-140.
34.Kehrl JH & Fauci AS (1983) Activation of human B lymphocytes after immunization with pneumococcal polysaccharides. J Clin Invest 71:1032-1040.
35.Baxendale HE, et al. (2000) Immunogenetic analysis of the immune response to pneumococcal polysaccharide. Eur J Immunol 30:1214-1223.
36.Taillardet M, et al. (2009) The thymus-independent immunity conferred by a pneumococcal polysaccharide is mediated by long-lived plasma cells. Blood 114:4432-4440.
37.McIntyre PB, et al. (2012) Effect of vaccines on bacterial meningitis worldwide. Lancet 380:1703-1711.
38.Jennings HJ, et al. (1977) Strucutres of the capsular polysaccharides of Neisseria meningitidis as determined by 13C-nuclear magnetic resonance spectroscopy. J Infect Dis 136 Suppl:S78-83.
39.Mond JJ, et al. (1995) T cell-independent antigens type 2. Annu Rev Immunol 13:655-692.
40.Snapper CM & Mond JJ (1996) A model for induction of T cell-independent humoral immunity in response to polysaccharide antigens. J Immunol 157:2229-2233.
41.Kirvan CA, et al. (2003) Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nat Med 9:914-920.
42.Cunningham MW (2012) Streptococcus and rheumatic fever. Curr Opin Rheumatol 24:408-416.
43.Yuki N, et al. (2004) Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci U S A 101:11404-11409.
44.Yuki N (2012) Guillain-Barre syndrome and anti-ganglioside antibodies: a clinician-scientist''s journey. Proc Jpn Acad Ser B Phys Biol Sci 88:299-326.
45.Chiba A, et al. (1992) Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome. Ann Neurol 31:677-679.
46.Nelson DS (1977) Autoantibodies in cancer patients. Pathology 9:155-160.
47.Seiner M, et al. (1975) Antinuclear reactivity of sera in patients with leukemia and other neoplastic diseases. Clin Immunol Immunopathol 4:374-381.
48.Thomas PJ, et al. (1983) Antinuclear, antinucleolar, and anticytoplasmic antibodies in patients with malignant melanoma. Cancer Res 43:1372-1380.
49.Crawford LV, et al. (1982) Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 30:403-408.
50.Chambers JC & Keene JD (1985) Isolation and analysis of cDNA clones expressing human lupus La antigen. Proc Natl Acad Sci U S A 82:2115-2119.
51.Magnani JL (1984) Carbohydrate differentiation and cancer-associated antigens detected by monoclonal antibodies. Biochem Soc Trans 12:543-545.
52.Tyers M & Mann M (2003) From genomics to proteomics. Nature 422:193-197.
53.Naour FL, et al. (2002) Identification of tumor-associated antigens using proteomics. Technol Cancer Res Treat 1:257-262.
54.Preiss S, et al. (2005) Tumor-induced antibodies resemble the response to tissue damage. Int J Cancer 115:456-462.
55.Feizi T (1985) Carbohydrate antigens in human cancer. Cancer Surv 4:245-269.
56.Giannini SL, et al. (2006) Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine 24:5937-5949.
57.Cupps TR, et al. (1984) Activation of human peripheral blood B cells following immunization with hepatitis B surface antigen vaccine. Cell Immunol 86:145-154.
58.Slovin SF, et al. (2005) Carbohydrate vaccines as immunotherapy for cancer. Immunol Cell Biol 83:418-428.
59.Harris JR & Markl J (1999) Keyhole limpet hemocyanin (KLH): a biomedical review. Micron 30:597-623.
60.Kensil CR, et al. (1991) Separation and characterization of saponins with adjuvant activity from Quillaja saponaria Molina cortex. J Immunol 146:431-437.
61.Canevari S, et al. (1983) Immunochemical analysis of the determinant recognized by a monoclonal antibody (MBr1) which specifically binds to human mammary epithelial cells. Cancer Res 43:1301-1305.
62.Bremer EG, et al. (1984) Characterization of a glycosphingolipid antigen defined by the monoclonal antibody MBr1 expressed in normal and neoplastic epithelial cells of human mammary gland. J Biol Chem 259:14773-14777.
63.Gilewski T, et al. (2001) Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial. Proc Natl Acad Sci U S A 98:3270-3275.
64.Huang YL, et al. (2013) Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer. Proc Natl Acad Sci U S A 110:2517-2522.
65.Lai CY, et al. (2010) Immunomodulatory and adjuvant activities of a polysaccharide extract of Ganoderma lucidum in vivo and in vitro. Vaccine 28:4945-4954.
66.Hsieh YS, et al. (2008) Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense. Bioorg Med Chem 16:6054-6068.
67.Harris PJ, et al. (1984) An improved procedure for the methylation analysis of oligosaccharides and polysaccharides. Carbohydr Res 127:59-73.
68.Lau E & Bacic A (1993) Capillary Gas-Chromatography of Partially Methylated Alditol Acetates on a High-Polarity, Cross-Linked, Fused-Silica Bpx70 Column. Journal of Chromatography 637:100-103.
69.Lu H, et al. (2003) A water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia suppresses azoxymethane-induction of colon cancers in male F344 rats. Oncol Rep 10:375-379.
70.Gao Y, et al. (2005) Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer. J Med Food 8:159-168.
71.Cao QZ & Lin ZB (2004) Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide. Acta Pharmacol Sin 25:833-838.
72.Wang PY, et al. (2012) Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum. Front Pharmacol 3:135.
73.Menard S, et al. (1983) Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res 43:1295-1300.
74.Slovin SF, et al. (1999) Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man. Proc Natl Acad Sci U S A 96:5710-5715.
75.Hakomori S (2003) Structure, organization, and function of glycosphingolipids in membrane. Curr Opin Hematol 10:16-24.
76.Clausen H, et al. (1985) Repetitive A epitope (type 3 chain A) defined by blood group A1-specific monoclonal antibody TH-1: chemical basis of qualitative A1 and A2 distinction. Proc Natl Acad Sci U S A 82:1199-1203.
77.Clausen H, et al. (1986) Novel blood group H glycolipid antigens exclusively expressed in blood group A and AB erythrocytes (type 3 chain H). II. Differential conversion of different H substrates by A1 and A2 enzymes, and type 3 chain H expression in relation to secretor status. J Biol Chem 261:1388-1392.
78.Cui Y, et al. (1993) Human cervical epidermal carcinoma-associated intracellular localization of glycosphingolipid with blood group A type 3 chain. Jpn J Cancer Res 84:664-672.
79.Kurimoto S, et al. (1995) Detection of a glycosphingolipid antigen in bladder cancer cells with monoclonal antibody MRG-1. Histochem J 27:247-252.
80.Stathopoulos GT, et al. (2008) A central role for tumor-derived monocyte chemoattractant protein-1 in malignant pleural effusion. J Natl Cancer Inst 100:1464-1476.
81.Fridlender ZG, et al. (2011) Monocyte chemoattractant protein-1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells. Am J Respir Cell Mol Biol 44:230-237.
82.Wang CC, et al. (2008) Glycan microarray of Globo H and related structures for quantitative analysis of breast cancer. Proc Natl Acad Sci U S A 105:11661-11666.
83.Baldus SE, et al. (1996) Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I). Glycoconj J 13:585-590.
84.Mollicone R, et al. (1996) Recognition of the blood group H type 2 trisaccharide epitope by 28 monoclonal antibodies and three lectins. Glycoconj J 13:263-271.
85.Lombard Y, et al. (1994) A new method for studying the binding and ingestion of zymosan particles by macrophages. J Immunol Methods 174:155-165.
86.Foote JB & Kearney JF (2009) Generation of B cell memory to the bacterial polysaccharide alpha-1,3 dextran. J Immunol 183:6359-6368.
87.Martin F, et al. (2001) Marginal zone and B1 B cells unite in the early response against T-independent blood-borne particulate antigens. Immunity 14:617-629.
88.Alquini G, et al. (2004) Polysaccharides from the fruit bodies of the basidiomycete Laetiporus sulphureus (Bull.: Fr.) Murr. FEMS Microbiol Lett 230:47-52.
89.Miyazaki T & Nishijima M (1981) Studies on fungal polysaccharides. XXVII. Structural examination of a water-soluble, antitumor polysaccharide of Ganoderma lucidum. Chem Pharm Bull (Tokyo) 29:3611-3616.
90.Axelsson K, et al. (1971) Polysaccharides elaborated by Fomes annosus (Fr.) Cooke. II. Neutral polysaccharides from the fruit bodies. Isolation and purification of a fucoxylomannan by precipitation with the H-agglutinin from eel-serum. Acta Chem Scand 25:3645-3650.
91.Ye L, et al. (2008) Structural elucidation of the polysaccharide moiety of a glycopeptide (GLPCW-II) from Ganoderma lucidum fruiting bodies. Carbohydr Res 343:746-752.


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