Protective effects of a protein-bound polysaccharide, PSK, on Candida albicans infection in mice via tumor necrosis factor-alpha induction.
We investigated the protective mechanism of a protein-bound polysaccharide, PSK, against lethal infection with Candida albicans (C. albicans) in mice. (1) In BALB/c mice inoculated intravenously with C. albicans, the intraperitoneal (ip) administration of PSK increased survival rates and prolonged the survival period depending on the time of administration, the dosage, and the size of fungal inoculum; the maximal effect was obtained when PSK 250 mg/kg was ip administered to mice 24 h before inoculation of 1 x 10(6) C. albicans (30 days survivors showed 60% and the mean survival period of mice with fatal infection increased 209%). (2) The protective effect of PSK was significantly decreased in mice treated with cyclophosphamide or carrageenan, or in mice treated previously with anti-tumor necrosis factor-alpha (TNF-alpha) antibody. (3) The administration of PSK significantly enhanced the expression of TNF-alpha gene in spleen and increased leukocyte functions from 6 h to 1 day after inoculation. (4) When the PSK fraction subjected to hydrolysis with beta1-3 glucanase or hydrazine was used instead of PSK, the anti-fungal activities were significantly decreased. These findings suggested that the protective effect of PSK on lethal C. albicans infection in mice was mainly produced via TNF-alpha functions, and that beta 1-3 glucan and protein moiety in PSK molecule were involved in the expression of the activities.
Ohmura
Y
Y
Biomedical Research Laboratory, Kureha Chemical Industry, Co Ltd, Tokyo, Japan.
Matsunaga
K
K
Motokawa
I
I
Sakurai
K
K
Ando
T
T
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D004731:Endotoxins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005122:Exudates and Transudates / Q000166:cytology / Q000187:drug effects; D005260:Female; D007155:Immunologic Factors / Q000627:therapeutic use*; D007202:Indicators and Reagents; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010587:Phagocytosis / Q000187:drug effects; D011134:Polysaccharides / Q000378:metabolism; D011509:Proteoglycans / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D004791:Enzyme Inhibitors; D007155:Immunologic Factors; D007202:Indicators and Reagents; D011134:Polysaccharides; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; C010770:polysaccharide-K; D019001:Nitric Oxide Synthase