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(Journal of Leukocyte Biology. 2002;72:207-216.)
© 2002 by Society for Leukocyte Biology

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

Ming-Jen Hsu^*, Shiuh-Sheng Lee and Wan-Wan Lin^*

^* Department of Pharmacology, College of Medicine, National Taiwan University, Taipei; and
Department of Biochemistry, National Yang-Ming University, Taipei, Taiwan

Correspondence: Wan-Wan Lin, National Taiwan University, Department of Pharmacology, College of Medicine, No. 1, Sec. 1, Jen-Ai Road, Taipei, Taiwan. E-mail: wwl{at}ha.mc.ntu.edu.tw

Ganoderma lucidum has been widely used as a remedy to promote health and longevity in China. The polysaccharide component with a branched (13)-ß-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.

Key Words: neutrophil apoptosis • PS-G • caspase activation • human

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