Acidic polysaccharide isolated from Phellinus linteus enhances through the up-regulation of nitric oxide and tumor necrosis factor-alpha from peritoneal macrophages.
Medicinal mushrooms are increasingly used to treat a wide variety of disease processes. Aqueous extract from the fruiting body or mycelia of Phellinus linteus has been reported to produce antitumor and immunomodulatory activities in vivo and in vitro. However, the mechanisms underlying its tumoricidal effects are poorly understood. The tumoricidal activity of peritoneal macrophages (PM) cultured with acidic polysaccharide (PL) isolated from Phellinus linteus against B16 melanoma cells was enhanced in a dose-dependent manner; growth inhibition increased 4-fold with 200 microg/ml of PL. To further characterize the mechanisms of PL, we investigated the effects of PL on phagocytosis and the release of nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen intermediates (ROI). To investigate the phagocytosis of PM, the uptake of Dextran (Dex)-FITC between PL-untreated and PL-treated PM was compared. We found some augment in phagocytosis of PL-treated PM compared untreated group. PL stimulated a dose-dependent increase in NO and TNF-alpha, but not in ROI production in PM. We suggested that PL has cytotoxicity against Yac-1 cells through the up-regulation of NO and TNF-alpha production. Also, PL enhanced the expression of costimulatory molecules, CD80 and CD86, and major histocompatibility complex (MHC) molecules II in PM. The ability of PL upon the up-regulation of these surface molecules involved in antigen-presenting processes may, by inference, activate T-cell-mediated immunity against malignant cells in vivo. Taken together, these results suggest that PL act as an effective immunomodulator and enhances the anti-tumoral activity of PM.
Kim
Gi-Young
GY
Department of Microbiology, Pusan National University College of Medicine, Ami-dong 1-10, Pusan 602-739, South Korea.
Choi
Gap-Seong
GS
Lee
Sang-Hee
SH
Park
Yeong-Min
YM
D000363:Agaricales / Q000737:chemistry*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D011134:Polysaccharides / Q000302:isolation & purification* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide