Sparassis crispa Fr. in an edible mushroom recently cultivable in Japan. A branched beta-glucan from S. crispa (SCG) is a major 6-branched 1,3-beta-D-glucan showing antitumor activity. In this study, we examined interferon-gamma (IFN-gamma) induction by SCG from splenocytes in DBA/2 mice in vitro. In the splenocytes derived from almost all inbred strains of mice except for DBA/1 and DBA/2 mice, IFN-gamma production was not induced by SCG. The breeder and genders of DBA/2 mice showed no influence on IFN-gamma induction by SCG. On the other hand, the magnitude of IFN-gamma induction was lower in young mice than in their older counterparts. IFN-gamma was induced by SCG in adherent splenocytes, but IFN-gamma production was most significantly increased by SCG in instances involving coexistence of adherent and nonadherent splenocytes. In fact, inhibition of cell-cell contact reduced IFN-gamma induction by SCG. In addition, interleukin-12 p70 (IL-12p70) was induced by SCG in DBA/2 mice. It was suggested that soluble factors and cell-cell contact mediate synergistic effects on SCG-induced IFN-gamma production.

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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Sparassis crispa Fr. is an edible/medicinal mushroom that recently became cultivable in Japan. SCG is a major 6-branched 1,3-beta-D-glucan in S. crispa showing antitumor activity. We recently found that the splenocytes from naive DBA/1 and DBA/2 mice strongly react with SCG to produce interferon-gamma (IFN-gamma). In this study, cytokines induced by SCG were screened and found to be IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-12 (IL-12p70). The addition of recombinant murine GM-CSF (rMuGM-CSF) to spleen cell cultures from various strains of mice synergistically enhanced IFN-gamma, TNF-alpha and IL-12p70 in the presence of SCG. In contrast, neutralizing GM-CSF using anti-GM-CSF monoclonal antibody (mAb) significantly inhibited IFN-gamma, TNF-alpha, and IL-12p70 elicited by SCG. We conclude that GM-CSF is a key molecule for cytokine induction by beta-glucan, and GM-CSF induction by SCG is the specific step in DBA/2 mice in vitro.

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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

A branched beta-glucan from Sparassis crispa (SCG) is a major 6-branched 1,3-beta-D-glucan showing antitumor activity. In the present study, we examined the anti-SCG antibody in naive mice by ELISA. Using SCG coated plate, sera of naive DBA/1 and DBA/2 mice contained significantly higher titers of antibody than other strains of mice. Anti-SCG Ab titers of each DBA/1 and DBA/2 mice were significantly varied. Using various polysaccharide-coated plate, sera of DBA/2 mice also reacted with a beta-glucan from Candida spp. (CSBG) having 1,3-beta and 1,6-beta-glucosidic linkages. The SCG specific immunoglobulin (Ig) M but G was detected in sera. The reactivity of sera to coated SCG was neutralized by adding soluble SCG and CSBG as competitor. These results suggested that DBA/1 and DBA/2 strains carry specific and unique immunological characteristics to branched 1,3-/1,6-beta-glucan.