Acidic polysaccharide isolated from Phellinus linteus induces nitric oxide-mediated tumoricidal activity of macrophages through protein tyrosine kinase and protein kinase C.
Mushroom polysaccharides are increasingly being utilized to treat a wide variety of diseases. Aqueous extracts from the Phellinus linteus have been reported to have anti-tumor and immunomodulatory properties. In particular, acidic polysaccharide (PL) isolated from P. linteus induced a secretory and cellular macrophage response. However, the exact mechanism by which PL regulates the macrophage functions remains unclear. PL-treated murine peritoneal macrophages in vitro and in vivo dramatically induced the production of NO. PL enhanced the lytic death of B16 cells through the production of NO. The present study examined signal molecules that may participate in PL-elicited responses by macrophages. The data demonstrated that a protein kinase C (PKC) inhibitor, staurosporine, and a protein tyrosine kinase (PTK) inhibitor, genistein, inhibited the tumoricidal activity of macrophages induced by PL. In addition, these inhibitors blocked the production of NO and the expression of surface molecules in PL-stimulated macrophages. Furthermore, CD11b/CD18 possibly mediates PL-induced cell activation. These results suggest that PL stimulates NO production for tumoricidal activity and induces cell-mediated immunity by increasing surface molecules, and the process may be a mechanism by which PL produces its therapeutic effects.
Kim
Gi-Young
GY
Department of Microbiology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea.
Oh
Yang-Hyo
YH
Park
Yeong-Min
YM
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001487:Basidiomycota / Q000737:chemistry / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D010537:Peritoneum / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011134:Polysaccharides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D011134:Polysaccharides; D009569:Nitric Oxide; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D019311:Staurosporine