Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1-->3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice.
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.
Laboratory of Immunophamacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
A
A
Tsuzuki
T
T
Tateishi
N
N
Ohno
Y
Y
Adachi
T
T
Yadomae
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D002236:Carbohydrate Conformation; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005936:Glucans / Q000737:chemistry / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis; D007958:Leukocyte Count; D007970:Leukopenia / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics; D051379:Mice; D008813:Mice, Inbred ICR; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012566:Sizofiran / Q000737:chemistry / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000235:genetics; D047071:beta-Glucans
D000970:Antineoplastic Agents; D016207:Cytokines; D017931:DNA Primers; D005936:Glucans; D015850:Interleukin-6; D012333:RNA, Messenger; D019089:Stem Cell Factor; D047071:beta-Glucans; D012566:Sizofiran; D016173:Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide; C033363:beta-1,3-glucan