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

SCG is a major 6‐branched 1,3‐β‐D‐glucan in Sparassis crispa Fr. SCG shows antitumor activity and also enhances the hematopoietic response in cyclophosphamide (CY)‐treated mice. In the present study, the molecular mechanism of the enhancement of the hematopoietic response was investigated. The levels of interferon‐ (IFN‐) γ, tumor necrosis factor‐ (TNF‐) α, granulocyte‐macrophage‐colony stimulating factor (GM‐CSF), interleukin‐ (IL‐) 6 and IL‐12p70 were significantly increased by SCG in CY‐treated mice. GM‐CSF production in the splenocytes from the CY‐treated mice was higher than that in normal mice regardless of SCG stimulation. Neutralizing GM‐CSF significantly inhibited the induction of IFN‐γ, TNF‐α and IL‐12p70 by SCG. The level of cytokine induction by SCG was regulated by the amount of endogenous GM‐CSF produced in response to CY treatment in a dose‐dependent manner. The expression of β‐glucan receptors, such as CR3 and dectin‐1, was up‐regulated by CY treatment. Blocking dectin‐1 significantly inhibited the induction of TNF‐α and IL‐12p70 production by SCG. Taken together, these results suggest that the key factors in the cytokine induction in CY‐treated mice were the enhanced levels of both endogenous GM‐CSF production and dectin‐1 expression.

[1]  Y. Adachi,et al.  Cell to cell contact through ICAM-1-LFA-1 and TNF-alpha synergistically contributes to GM-CSF and subsequent cytokine synthesis in DBA/2 mice induced by 1,3-beta-D-Glucan SCG. , 2006, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[2]  Y. Adachi,et al.  Soy isoflavone aglycone modulates a hematopoietic response in combination with soluble beta-glucan: SCG. , 2005, Biological & pharmaceutical bulletin.

[3]  Y. Adachi,et al.  Effect of Candida albicans cell wall glucan as adjuvant for induction of autoimmune arthritis in mice. , 2005, Journal of autoimmunity.

[4]  J. Schlom,et al.  Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. , 2005, Blood.

[5]  S. Gordon,et al.  Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. , 2005, Immunity.

[6]  S. Akira,et al.  A role for fungal β-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice , 2005, The Journal of experimental medicine.

[7]  Y. Adachi,et al.  Activation of Toll-Like Receptor-Mediated NF-κβ by Zymosan-Derived Water-Soluble Fraction: Possible Contribution of Endotoxin-Like Substances , 2005 .

[8]  Y. Adachi,et al.  Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates cytokine induction by 1,3-beta-D-glucan SCG in DBA/2 mice in vitro. , 2004, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[9]  Jun Yan,et al.  Mechanism by Which Orally Administered β-1,3-Glucans Enhance the Tumoricidal Activity of Antitumor Monoclonal Antibodies in Murine Tumor Models1 , 2004, The Journal of Immunology.

[10]  T. Ishii,et al.  Characterization of β-Glucan Recognition Site on C-Type Lectin, Dectin 1 , 2004, Infection and Immunity.

[11]  S. Sakaguchi.  Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. , 2004, Annual review of immunology.

[12]  G. Ostroff,et al.  Beta-glucan functions as an adjuvant for monoclonal antibody immunotherapy by recruiting tumoricidal granulocytes as killer cells. , 2003, Cancer research.

[13]  S. Gordon,et al.  Dectin-1 Expression and Function Are Enhanced on Alternatively Activated and GM-CSF-Treated Macrophages and Are Negatively Regulated by IL-10, Dexamethasone, and Lipopolysaccharide , 2003, The Journal of Immunology.

[14]  Y. Togashi,et al.  Critical role of the Th1/Tc1 circuit for the generation of tumor‐specific CTL during tumor eradication in vivo by Th1‐cell therapy , 2003, Cancer science.

[15]  Y. Adachi,et al.  Antibody to Soluble 1,3/1,6-β-D-Glucan, SCG in Sera of Naive DBA/2 Mice , 2003 .

[16]  Y. Adachi,et al.  Immunomodulating Activity of a b -Glucan Preparation, SCG, Extracted from a Culinary–Medicinal Mushroom, Sparassis crispa Wulf.:Fr. (Aphyllophoromycetideae), and Application to Cancer Patients , 2003 .

[17]  C. Sousa.  Faculty Opinions recommendation of Dectin-1 mediates the biological effects of beta-glucans. , 2003 .

[18]  S. Gordon,et al.  Dectin-1 Mediates the Biological Effects of β-Glucans , 2003, The Journal of experimental medicine.

[19]  Y. Adachi,et al.  Enhanced Cytokine Synthesis of Leukocytes by a β‐Glucan Preparation, SCG, Extracted from a Medicinal Mushroom, Sparassis crispa , 2003, Immunopharmacology and immunotoxicology.

[20]  Y. Adachi,et al.  IFN-γ Induction by SCG, 1,3-β-D-Glucan from Sparassis crispa, in DBA/2 Mice In Vitro , 2002 .

[21]  K. Takenaka,et al.  Predictive value of circulating immature cell counts in peripheral blood for timing of peripheral blood progenitor cell collection after G–CSF plus chemotherapy‐induced mobilization , 2002, Transfusion.

[22]  Y. Adachi,et al.  Effect of SCG, 1,3-beta-D-glucan from Sparassis crispa on the hematopoietic response in cyclophosphamide induced leukopenic mice. , 2002, Biological & pharmaceutical bulletin.

[23]  R. Offringa,et al.  Cyclophosphamide enhances anti‐tumor effect of wild‐type p53‐specific CTL , 2000, International journal of cancer.

[24]  N. Ohno,et al.  Antitumor 1,3-β-Glucan from Cultured Fruit Body of Sparassis crispa , 2000 .

[25]  N. Ohno,et al.  Enhancement of IL-8 production from human monocytic and granulocytic cell lines, THP-1 and HL-60, stimulated with Malassezia furfur. , 2000, FEMS immunology and medical microbiology.

[26]  Y. Adachi,et al.  Immunopharmacological and immunotoxicological activities of a water-soluble (1-->3)-beta-D-glucan, CSBG from Candida spp. , 2000, International journal of immunopharmacology.

[27]  T. Yadomae.  真菌β-1,3-グルカンの構造と生物活性 , 2000 .

[28]  Y. Adachi,et al.  Inflammatory and immunopharmacological activities of meta-periodate oxidized zymosan. , 1999, Zentralblatt fur Bakteriologie : international journal of medical microbiology.

[29]  N. Ohno,et al.  Immunomodulation by hot water and ethanol extracts of Ganoderma lucidum , 1998 .

[30]  J. Norton,et al.  Immune response against large tumors eradicated by treatment with cyclophosphamide and IL-12. , 1998, Journal of immunology.

[31]  Y. Adachi,et al.  Nitric Oxide Synthesis in Murine Peritoneal Macrophages by Fungal β-Glucans , 1997 .

[32]  C. Hiramine,et al.  Thymic nurse cells as the site of thymocyte apoptosis and apoptotic cell clearance in the thymus of cyclophosphamide-treated mice. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[33]  V. Vetvicka,et al.  Soluble beta-glucan polysaccharide binding to the lectin site of neutrophil or natural killer cell complement receptor type 3 (CD11b/CD18) generates a primed state of the receptor capable of mediating cytotoxicity of iC3b-opsonized target cells. , 1996, The Journal of clinical investigation.

[34]  V. Vetvicka,et al.  Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). , 1996, Journal of immunology.

[35]  Y. Adachi,et al.  Enhancement of cytokine production by macrophages stimulated with (1-->3)-beta-D-glucan, grifolan (GRN), isolated from Grifola frondosa. , 1994, Biological & pharmaceutical bulletin.

[36]  J. Nemoto,et al.  Immunopharmacological characterization of a highly branched fungal (1-->3)-beta-D-glucan, OL-2, isolated from Omphalia lapidescens. , 1993, Biological & pharmaceutical bulletin.

[37]  J. Lotem,et al.  Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. , 1992, Blood.

[38]  D. Metcalf,et al.  The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells , 1989, Nature.

[39]  C. R. Clark,et al.  Granulocyte/macrophage colony-stimulating factor stimulates monocyte and tissue macrophage proliferation and enhances their responsiveness to macrophage colony-stimulating factor. , 1988, Blood.

[40]  N. Ohno,et al.  Antitumor activity of a highly branched (1----3)-beta-D-glucan, SSG, obtained from Sclerotinia sclerotiorum IFO 9395. , 1987, Journal of pharmacobio-dynamics.

[41]  N. Ohno,et al.  Purification, antitumor activity, and structural characterization of beta-1,3-glucan from Peziza vesiculosa. , 1985, Chemical & pharmaceutical bulletin.

[42]  K. Austen,et al.  Properties of glycans that activate the human alternative complement pathway and interact with the human monocyte beta-glucan receptor. , 1985, Journal of immunology.

[43]  K. Orita,et al.  [Clinical evaluation of SPG (schizophyllan) as a therapeutic adjuvant after surgery of gastric cancer--controlled study by an envelope method]. , 1983, Gan to kagaku ryoho. Cancer & chemotherapy.

[44]  S. Morikawa,et al.  Enhancement of delayed hypersensitivity by depletion of suppressor T cells with cyclophosphamide in mice , 1976, Nature.

[45]  B. Fox.  A Review of Cyclophosphamide , 1975, British Journal of Cancer.

[46]  W. M. Fosdick,et al.  Long-term cyclophosphamide therapy in rheumatoid arthritis. , 1968, Arthritis and rheumatism.

[47]  吉富 啓之.  A role for fungal β-glucans and their receptor dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice , 2005 .

[48]  Y. Adachi,et al.  Activation of toll-like receptor-mediated NF-kappa beta by zymosan-derived water-soluble fraction: possible contribution of endotoxin-like substances. , 2005, Immunopharmacology and immunotoxicology.

[49]  Yuji Togashi,et al.  Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2 , 2004, Cancer Immunology, Immunotherapy.

[50]  Shigenori Tanaka,et al.  Characterization of beta-glucan recognition site on C-type lectin, dectin 1. , 2004, Infection and immunity.

[51]  Y. Adachi,et al.  Antibody to soluble 1,3/1,6-beta-D-glucan, SCG in sera of naive DBA/2 mice. , 2003, Biological & pharmaceutical bulletin.

[52]  Y. Adachi,et al.  Antitumor Activity and Hematopoietic Response of a b -Glucan Extracted from an Edible and Medicinal Mushroom Sparassis crispa Wulf.: Fr. (Aphyllophoromycetideae) , 2002 .

[53]  Y. Adachi,et al.  IFN-gamma induction by SCG, 1,3-beta-D-glucan from Sparassis crispa, in DBA/2 mice in vitro. , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[54]  T. Yadomae.  [Structure and biological activities of fungal beta-1,3-glucans]. , 2000, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[55]  N. Ohno,et al.  Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa. , 2000, Biological & pharmaceutical bulletin.

[56]  Y. Adachi,et al.  Nitric oxide synthesis in murine peritoneal macrophages by fungal beta-glucans. , 1997, Biological & pharmaceutical bulletin.

[57]  J. Van Snick.  Interleukin-6: an overview. , 1990, Annual review of immunology.

[58]  T. Taguchi,et al.  Clinical efficacy of lentinan on neoplastic diseases. , 1983, Advances in experimental medicine and biology.