laminaran and Leukopenia

Sparassis crispa Fr. is an edible mushroom recently cultivable in Japan. It contains a remarkably high content of 6-branched 1,3-beta-D-glucan showing antitumor activity. Using ion-exchange chromatography, a purified beta-glucan preparation, SCG, was prepared. In this study, we examined the hematopoietic response by SCG in cyclophosphamide (CY)-induced leukopenic mice. SCG enhanced the hematopoietic response in CY induced leukopenic mice by intraperitoneal routes over a wide range of concentrations. SCG enhanced the hematopoietic response in CY-treated mice by prior or post administration. Analyzing the leukocyte population by flow cytometry, monocytes and granulocytes in the peritoneal cavity, liver, spleen and bone marrow (BM) recovered faster than in the control group. The ratio of natural killer cells and gammadelta T cells in the liver, spleen and peritoneal cavity was also increased. In contrast, CD4+ CD8+ cells in the thymus were temporarily significantly decreased by the administration of SCG. Interleukin-6 (IL-6) production of CY+SCG-treated peritoneal exdated cells (PECs), spleen cells and bone marrow cells (BMCs) were higher than that of the CY-treated group. By in vitro culture of CY-treated PEC and spleen cells, IL-6 production was enhanced by the addition of SCG. These facts suggested the possibility that IL-6 might be a key cytokine for the enhanced hematopoietic response by SCG.

Topics: Animals; beta-Glucans; Cell Count; Cyclophosphamide; Disease Models, Animal; Dose-Response Relationship, Drug; Glucans; Injections, Intraperitoneal; Interleukin-6; Leukocytes; Leukopenia; Male; Mice; Mice, Inbred ICR; Organ Specificity; Polyporales

Sparassis crispa is an edible mushroom recently cultivable in Japan. Polysaccharide fractions were prepared from the cultured S. crispa by repeated extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA). HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol-precipitable fractions. By chemical, enzymic, and NMR analyses, the primary structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one branch in approximately every third mainchain unit. All of these fractions showed antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong vascular dilation and hemorrhage reaction. These fractions also showed enhanced hematopoietic response to cyclophosphamide induced leukopenic mice following intraperitoneal or peroral administration.

Topics: Animals; Antineoplastic Agents; beta-Glucans; Disease Models, Animal; Drug Screening Assays, Antitumor; Glucans; Leukocyte Count; Leukopenia; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred ICR; Polyporales; Polysaccharides; Sarcoma 180; Structure-Activity Relationship

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.

Topics: Animals; Antineoplastic Agents; Base Sequence; beta-Glucans; Carbohydrate Conformation; Colony-Forming Units Assay; Cyclophosphamide; Cytokines; DNA Primers; Gene Expression; Glucans; Hematopoiesis; Interleukin-6; Leukocyte Count; Leukopenia; Macrophage Colony-Stimulating Factor; Mice; Mice, Inbred ICR; RNA, Messenger; Sizofiran; Stem Cell Factor