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Cell surface changes of in situ macrophages induced by superimposed antigen.

Mice received an injection of sheep erythrocytes (SRBC) into the footpad ” prepared” or “not prepared” with a 7-day-prior injection of a protein-bound polysaccharide from Coriolus versicolor (PSK; Krestin), and the ultrastructure of in situ macrophages was studied at various intervals after the injection. A single SRBC injection into the footpad induced linear cell arrangements of several macrophages. The macrophages showed no prominent morphological alterations after SRBC digestion. When PSK-stimulated subcutaneous macrophages were challenged by SRBC, they rapidly sent out numerous long cytoplasmic projections which radiated in all directions. Such projections of neighboring macrophages tended to contact one another. At the following stage, a pronounced sequential alteration was noted, characterized by the interlocking of elongated projections. This provided massive aggregations of “activated” macrophages. These observations suggest the possibility that intercellular communication among “activated” macrophages was elicited, particularly in the subcutaneous region, and maintained through an intensive interaction of cytoplasmic projections. Further, the present results histologically support our previous report which shows that the “PSK-prepared” footpad site but not the “prepared” one supports development of a splenic humoral immune response following injection of superimposed SRBC.[…]

Effects of a protein-bound polysaccharide from a basidiomycetes against hepatocarcinogenesis induced by 3′-methyl-4-dimethylaminoazobenzene in rats.

PSK, extracted from mycelia of a strain of Coriolus versicolor, was administered to groups of 20 male Wistar rats before and during treatment with 3′-methyl-4-dimethylaminoazobenzene (3-MDAB). After 24 weeks, the survival rates were significantly higher in the groups given PSK before or with the 3-MDAB than in groups not given PSK or given PSK after 12 weeks of 3-MDAB treatment. Blood alpha-fetoprotein levels, determined every four weeks, increased in all groups after 3-MDAB treatment, but were significantly lower in the groups given PSK before or with the 3-MDAB than in the other groups. The results indicate that PSK had a suppressive effect on 3-MDAB-induced hepatocarcinogenesis.[…]

Chloromethane, Methyl Donor in Veratryl Alcohol Biosynthesis in Phanerochaete chrysosporium and Other Lignin-Degrading Fungi.

Chloromethane, a gaseous natural product implicated in methylation processes in Phellinus pomaceus, has been shown to act as methyl donor in veratryl alcohol biosynthesis in the lignin-degrading fungi Phanerochaete chrysosporium, Phlebia radiata, and Coriolus versicolor, none of which released detectable amounts of CH(3)Cl during growth. When P. chrysosporium was grown in a medium containing CH(3)Cl, levels of CH(3) incorporation into the 3- and 4-O-methyl groups of veratryl alcohol were very high and initially similar to those observed when the medium was supplemented with l-[methyl-H(3)]methionine. When CH(3)Cl was added to cultures actively synthesizing veratryl alcohol, incorporation of CH(3) was very rapid, with 81% of veratryl alcohol labeled after 12 h. By contrast, incorporation of CH(3) from l-[methyl-H(3)]methionine was comparatively slow, attaining 10% after 12 h. It is proposed that these lignin-degrading fungi possess a tightly channeled multienzyme system in which CH(3)Cl biosynthesis is closely coupled to CH(3)Cl utilization for methylation of veratryl alcohol precursors.[…]

Induction of immunopotentiation activity by a protein-bound polysaccharide, PSK (review).

A protein-bound polysaccharide, PSK, extracted from the mycelium of Coriolus versicolor (Fr.) Quel, has been recognized for its host-mediated induction of antitumor and antimicrobial activities in mice. Intravenous administration of PSK, in association with OK-432 (Picibanil), transiently induced endogenous production of a cytotoxic factor (CF) (possibly tumor necrosis factor, TNF) in normal mice. The ability to produce CF depended greatly on both dose and interval between administration of the PSK and OK-432. Although PSK has been reported to contain several active ingredients, unfractionated PSK has been used in almost all experiments performed so far. We recently reported that, of the four subfractions separated by successive filtration through membrane filters, only the highest molecular weight fraction F4 (MW greater than 200 kD) induced significant antimicrobial activity in mice. PSK stimulated the NBT-reducing activity of mouse peritoneal macrophages and the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood polymorphonuclear cells (PMN). Among the subfractions of PSK, the highest molecular weight fraction F4, and the fraction precipitated at pH 4.0-4.5 (Fr. 4), stimulated macrophage NBT-reducing activity and PMN iodination most. In contrast, natural and chemically modified glucans had little or no stimulating activity. PSK, F4 or Fr. 4 additively or synergistically stimulated TNF-induced cytotoxicity against L-929 cells, differentiation of human myelogenous leukemia cell lines toward monocytes/macrophages, and iodination of human peripheral blood PMN. The active PSK subfractions significantly reduced the down regulation of specific 125I-TNF or 125I-IFN-gamma binding to cellular receptors. These data suggest that (i) immunopotentiation activity of PSK might be ascribed, at least in part, to stimulation of cytokine action and production, and (ii) PSK might have some unique structural features.[…]

A protein-bound polysaccharide immunomodulator, PSK, does not suppress the conversion from 1-(2-tetrahydrofuryl)-5-fluorouracil to 5-fluorouracil in patients with gastric cancer.

Effects of the immunomodulator PSK on the metabolism of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) to 5-fluorouracil (5-FU) were examined in 10 patients with advanced gastric cancer and who had undergone curative resection. PSK is a protein-bound preparation, extracted from Coriolus versicolor and belongs to Basidiomycetes. The 5-FU concentration in the plasma was 0.024 micrograms/ml at 15 min after the intravenous injection of 400 mg of tegafur and the area under the curve of 5-FU was 0.58 micrograms.h/ml. Following administration of PSK, 3 g/day for 8-14 months, there was no change in the plasma level of 5-FU, in any patient. As the clinical dose of PSK had no apparent influence on the metabolism of tegafur to 5-FU, the combination of PSK and tegafur can be prescribed to treat patients with advanced gastric cancer.[…]

Functional maturation of monocytes/macrophages induced by PSK subfractions.

When mouse resident peritoneal macrophages were cultured with PSK (Krestin), a protein-bound polysaccharide extracted from Coriolus versicolor, they became enlarged and elongated and expressed higher NBT-reducing activity. PSK stimulated the production of differentiation-inducing factor and cytotoxic factor by the mouse macrophage-like cell line J774.1, and iodination (incorporation of radioactive iodine into an acid-insoluble fraction) and interleukin-1-like factor production by human peripheral blood monocytes. Among four different PSK subfractions, the highest molecular weight fraction (MW greater than 200 kD) was the most potent. Natural and chemically modified glucans had little or no activity. The data suggest that some unique structure of the highest molecular weight fraction of PSK directly stimulates the monocytes/macrophages.[…]

Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.[…]

Mimicking of superoxide dismutase activity by protein-bound polysaccharide of Coriolus versicolor QUEL, and oxidative stress relief for cancer patients.

The protein-bound polysaccharide of Coriolus versicolor QUEL (PS-K) has been found to express antioxidant activity as an “ion-radical scavenger” in diamine oxidation reactions. The mode of this expression was examined to determine whether the drug functioned as a simple radical scavenger or mimicked the action of superoxide dismutase (SOD). The latter was confirmed in both enzymatic and nonenzymatic superoxide anion radical (O2-.) producing systems in vitro. The SOD mimetic activity of PS-K was demonstrated by quantitative analysis of hydrogen peroxide as the end product of O2-., its formation being assisted catalytically by SOD or PS-K. Analysis by electron spin resonance also confirmed the SOD mimetic activity of PS-K in a xanthine-xanthine oxidase reaction. Relative SOD activity with PS-K was approximately 1/8,000 in a KO2-O2-.-producing system. The SOD mimetic activity of PS-K resisted treatment by 0.7N HCl, 0.7N NaOH, boiling for 30 minutes in a double water bath, and digestion by pronase. Fractionation according to differences in molecular mass caused no significant increase in relative SOD activity within a certain range of molecular mass, indicating that there is no definite molecule expressing SOD mimetic activity. Tumor-bearing rats and human patients with digestive tract cancer who suffered from oxidative stress were relieved by a single intraperitoneal administration of PS-K or a 1-day peroral prescription.[…]

Manganese Peroxidase, Produced by Trametes versicolor during Pulp Bleaching, Demethylates and Delignifies Kraft Pulp.

Previous work has shown that Trametes (Coriolus) versicolor bleaches kraft pulp brownstock with the concomitant release of methanol. In this work, the fungus is shown to produce both laccase and manganese peroxidase (MnP) but not lignin peroxidase during pulp bleaching. MnP production was enhanced by the presence of pulp and/or Mn(II) ions. The maximum level of secreted MnP was coincident with the maximum rate of fungal bleaching. Culture filtrates isolated from bleaching cultures produced Mn(II)- and hydrogen peroxide-dependent pulp demethylation and delignification. Laccase and MnP were separated by ion-exchange chromatography. Purified MnP alone produced most of the demethylation and delignification exhibited by the culture filtrates. On the basis of the methanol released and the total and phenolic methoxyl contents of the pulp, it appears that MnP shows a preference for the oxidation of phenolic lignin substructures. The extensive increase in brightness observed in the fungus-treated pulp was not found with MnP alone. Therefore, either the MnP effect must be optimized or other enzymes or compounds from the fungus are also required for brightening.[…]

Reversal of inhibition of reactive oxygen species on respiratory burst of macrophages by polysaccharide from Coriolus versicolor.

Using a luminol-dependent, chemiluminescence assay we found tert-butylhydroperoxide to be a strong inhibitor of the respiratory burst of mouse peritoneal macrophages. However, the inhibition of respiratory burst induced by tert-butylhydroperoxide could be prevented after the interperitoneal injection of polysaccharide from Coriolus versicolor (PSK). Further investigation showed that glutathione peroxidase activity was markedly elevated in PSK-treated macrophages. After incubation with tert-butylhydroperoxide, higher activity of glutathione peroxidase was maintained in PSK-treated macrophages. These results suggest that the immunological function of macrophages is related to the activity of glutathione peroxidase. The non-specific immunopolysaccharide might protect macrophages from the damage induced by reactive oxygen species by enhancing antioxidative capacity.[…]