Nitric Oxide Synthesis in Murine Peritoneal Macrophages by Fungal .BETA.-Glucans.

Hashimoto, Tomoe; Ohno, Naohito; Adachi, Yoshiyuki; Yadomae, Toshiro

doi:10.1248/bpb.20.1006

Cited by 35 publications

(24 citation statements)

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“…We have long been working on the relationship between structure and immunomodulating activity of b-glucans, using G. frondosa, 11,12) P. vesiculosa, 13) S. sclerotiorum, 14,15) S. commune, 16) O. lapidescens, 17) G. lucidum, 18) S. cerevisiae, 19) C. albicans 20) and M. furfur. 21) During this period, we found the activity was significantly dependent on the molecular weight, degree of branching, and conformation, in a preclinical animal study.…”

Section: Discussionmentioning

confidence: 99%

Effect of SCG, 1,3-β-D-Glucan from Sparassis crispa on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Harada

Miura

Adachi

et al. 2002

Biological & Pharmaceutical Bulletin

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The major side-effect of most anti-cancer chemotherapeutic drugs is neutropenia, and the administration of these drugs impairs blood-forming functions (e.g. the generation of neutrophils, NK cells, etc.) that are important to maintain the defense systems of the patients. As a result, chemotherapy may accelerate the risk of tumor metastases and fungal infection. Metastasis of tumor cells is a serious concern, causing deterioration in the condition of patients receiving cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Effect of SCG, 1,3-β-D-Glucan from Sparassis crispa on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Harada

Miura

Adachi

et al. 2002

Biological & Pharmaceutical Bulletin

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“…We previously demonstrated that SPG and SPG-OH had different immunopharmacological properties, including blood clearance, 16) reactivity of limulus factor G, 17) and effects on NO synthesis by macrophages in vivo 18) and in vitro. 8,19) Regarding these ac- tivities, SPG was generally less effective than SPG-OH, suggesting that the single helical conformer is more effective in activation of host defense. Other b-glucans, GRN and SSG, are also reported to contain a single helical moiety.…”

Section: Discussionmentioning

confidence: 99%

“…7) GRN and SSG contain a mixture of single and triple helix conformers, whereas SPG is composed of triple helixes only. 8,9) The molecular weight of a single chain of SPG is 15 kDa, which is much lower than those of GRN (50 kDa) and SSG (200 kDa). 5,6,10) Our accumulated data suggest that the molecular weight, degree of branching, number of substituents, as well as ultrastructure, including the presence of single and triple helixes, significantly affects the biological activities of b-glucans.…”

Section: (1→6)-branched (1→3)-b-d-glucans (B-glucans) Frommentioning

confidence: 94%

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Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1.RAR.3)-.BETA.-Glucans from Fungi.

Suzuki

Adachi

Ohno

et al. 2001

Biological & Pharmaceutical Bulletin

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(1→6)-branched (1→3)-b-D-glucans (b-glucans) fromfungi are known to enhance various immunopharmacological activities such as antitumor activity.1) Some of them, including lentinan 2) and sonifilan (SPG), 3) have been used clinically for cancer therapy in Japan. We have been investigating various immunopharmacological effects of b-glucans, such as grifolan (GRN) from Grifola frondasa 4) and sclerotinia sclerotiorum glucan (SSG) 5) from Sclerotinia sclerotiorum IFO 9395, which were isolated originally by our group. GRN has a similar primary structure to SPG,4) but SSG consists of a b-(1→3)-polyglucose backbone with every second residue substituted with mono-glucosyl branches. 5,6) The ultrastructure of GRN and SSG is distinct from that of SPG.7) GRN and SSG contain a mixture of single and triple helix conformers, whereas SPG is composed of triple helixes only. 8,9) The molecular weight of a single chain of SPG is 15 kDa, which is much lower than those of GRN (50 kDa) and SSG (200 kDa). 5,6,10) Our accumulated data suggest that the molecular weight, degree of branching, number of substituents, as well as ultrastructure, including the presence of single and triple helixes, significantly affects the biological activities of b-glucans. [11][12][13][14] For instance, it was demonstrated that GRN and SSG could more markedly induce various activities of immunological cells such as cytotoxic T cells and macrophages than SPG, although the antitumor effects of these two glucans were similar to those of SPG.15) Using SPG and SPG-OH, which is a single helical conformer prepared by alkaline treatment of SPG, we also found previously that the biological activities of b-glucans, i.e. blood clearance, 16) reactivity of limulus factor G activation, 17) and NO synthesis in vivo 18) and in vitro, are strongly associated with their conformation. 8,19) However we do not yet know the details of activities of various b-glucans on helper T cell modulation.T cell responses have been divided in two subclasses, Th1and Th2, according to the profile of the lymphokines produced, i.e., IFN-g and IL-2 vs. IL-4, IL-5, and IL-10, respectively. 20) Evidence is accumulating that cytokines play a role during T helper cell differentiation. IL-4 has a direct effect on the induction of IL-4-producing Th2 cells 21) and IFN-g causes the preferential outgrowth of Th1. 22) In addition, IL-4 appears to inhibit the induction of Th1 cells in vitro and in vivo. 23,24) Antigen-presenting cells such as macrophages and dendritic cells also play a major role in T helper cell differentiation. IL-12 derived from antigen-presenting cells stimulates IFN-g production from T cells and NK cells, thereby favoring a Th1-pattern of response. 25,26) There is clear evidence that IL-12 can suppress IL-4 mRNA induction, both directly and indirectly, through induction of 28) In the antibody response, IgG2a responses are induced by IFNg and suppressed by IL-4. 29) IFN-g promotes isotype switching to IgG2a.30,31) IL-12 also stimulates the production of IgG2a, presumably through i...

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“…We have been studying the relationship between the structure and immunomodulating activity of β-glucans using G. frondosa (2), P. vesiculosa (26), S. sclerotiorum (31), S. commune (16), O. lapidescens (36), G. lucidum (33), S. cerevisiae (32), C. albicans (43), S. crispa (10-15, 28, 30, 34, 35) and M. furfur (39). β-Glucan is a component of fungi, and is used in immunotherapy as an immunomodulating substance, as a biological response modifier.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

Harada

Kawaminami

Miura

et al. 2006

Microbiology and Immunology

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Immunomodulating substances, biological response modifiers, and biotherapy, including immunotherapy, are important for the treatment of cancer. Some β-glucans are well-known biological response modifiers, and the mushrooms from which they are derived are widely distributed in nature and are used as medicine and food. Among the β-glucans, the 6-branched 1,3-β-glucan is the best characterized. Lentinan from Lentinus edodes (40) and Sonifilan (SPG) from Schizophyllum commune (9) have been used clinically for cancer therapy in Japan. We have analyzed the mechanism of β-glucanmediated immunopharmacological activity, and demonstrated the conformation-dependent and -independent activity of β-glucan (48, 49). Recent data indicated that orally administered β-1,3-glucan potentiated the activity of antitumor monoclonal antibody, leading to enhanced tumor regression and survival (20,21). Thus, cancer immunotherapy using β-glucan is a promising possibility.Sparassis crispa is a medicinal mushroom that recently became cultivatable in Japan. The primary component of the major cold NaOH-extracted polysaccharide fraction from S. crispa was found to be 6-branched 1,3-β-glucan, having one branch approximately every third main chain. This fraction showed strong antitumor activity against the solid form of Sarcoma 180 in ICR mice (34). In our recent study, we used S. crispa to treat several cancer patients in combination with lymphocyte transplantation immunotherapy and obtained a good response (35). To examine the pharmacological usefulness of S. crispa β-glucan Mechanism of Enhanced Hematopoietic

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Nitric Oxide Synthesis in Murine Peritoneal Macrophages by Fungal .BETA.-Glucans.

Cited by 35 publications

References 0 publications

Effect of SCG, 1,3-β-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Effect of SCG, 1,3-β-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1.RAR.3)-.BETA.-Glucans from Fungi.

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

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Nitric Oxide Synthesis in Murine Peritoneal Macrophages by Fungal .BETA.-Glucans.

Cited by 35 publications

References 0 publications

Effect of SCG, 1,3-&beta;-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Effect of SCG, 1,3-&beta;-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Th1/Th2-Balancing Immunomodulating Activity of Gel-Forming (1.RAR.3)-.BETA.-Glucans from Fungi.

Mechanism of Enhanced Hematopoietic Response by Soluble β‐Glucan SCG in Cyclophosphamide‐Treated Mice

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Product

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Effect of SCG, 1,3-β-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice

Effect of SCG, 1,3-β-<small>D</small>-Glucan from <i>Sparassis crispa</i> on the Hematopoietic Response in Cyclophosphamide Induced Leukopenic Mice