Polysaccharide purified from Ganoderma lucidum inhibits spontaneous and Fas-mediated apoptosis in human neutrophils through activation of the phosphatidylinositol 3 kinase/Akt signaling pathway

• Published in: Journal of leukocyte biology Vol. 72; no. 1; pp. 207 - 216
• Main Authors: Hsu, Ming‐Jen, Lee, Shiuh‐Sheng, Lin, Wan‐Wan
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.07.2002
• Subjects: Antioxidants - pharmacology; Apoptosis - drug effects; beta-Glucans; caspase activation; Caspase Inhibitors; Cell Nucleus - ultrastructure; Cells, Cultured; Cysteine Proteinase Inhibitors - pharmacology; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; fas Receptor - metabolism; Glucans - isolation & purification; Glucans - pharmacology; human; Humans; Kinetics; neutrophil apoptosis; Neutrophils - drug effects; Neutrophils - enzymology; Neutrophils - ultrastructure; Phosphatidylinositol 3-Kinases - metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; PS-G; Reishi - chemistry; Signal Transduction
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.72.1.207

Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (1→3)‐β‐D‐glucan moiety from G. lucidum (PS‐G) has shown evidence of enhancement of immune responses and of eliciting anti‐tumor effects. In this study, we investigated the effect of PS‐G on neutrophil viability, which is manifested by spontaneous apoptosis. Annexin V staining and MTT assays reveal that PS‐G is able to inhibit spontaneous and Fas‐induced neutrophil apoptosis, and this effect of PS‐G is enhanced by the presence of zVAD (a caspase inhibitor) and GM‐CSF. The antiapoptotic effect of PS‐G is diminished by the presence of wortmannin and LY294002 (two PI‐3K inhibitors), but is not altered by PD98059 (a MEK inhibitor). Western blotting indicates the stimulating effect of PS‐G on Akt phosphorylation and its inhibition of procaspase 3 degradation, which occurs in neutrophils undergoing spontaneous apoptosis or triggered death by Fas. Taken together, PS‐G elicitation of antiapoptotic effects on neutrophils primarily relies on activation of Akt‐regulated signaling pathways.