Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells.
Acidic polysaccharides (PL) isolated from Phellinus linteus are known to stimulate the proliferation of T lymphocytes and humoral immune functions to act as a polyclonal activator of B cells, and to inhibit tumor growth and metastasis. However, little is known about their immunomodulating effects or the effects of its mechanisms on murine bone marrow (BM)-derived dendritic cells (DC). In this study, it profoundly increased CD80, CD86, MHC I, and MHC II expression in murine, GM-CSF and IL-4 stimulated, BM-derived myeloid DC. The ability of unstimulated DC to uptake dextran was higher than that of PL- or LPS-stimulated DC. We analyzed the concentration of IL-12 secreted by DC using flow cytometry and ELISA. Untreated DC secreted a low concentration of IL-12, while PL- or LPS-stimulated DC secreted higher levels of IL-12 than untreated DC. There were no remarkable differences in the concentrations of IL-12 produced by PL- or LPS-stimulated DC. However, polymyxin B (PB; an LPS inhibitor) effectively inhibited the surface molecules and IL-12 production induced by LPS, but had no effect on the PL in DC. PL-treated DC were much more potent antigen-presenting cells in allogeneic immune response than untreated DC. PL treatment not only formed morphologically mature DC but also induced predominant migration to lymphoid tissues. Moreover, the inhibitors of protein tyrosine kinase (PTK) or protein kinase C (PKC) significantly blocked the expression of surface molecules and IL-12 production in PL-stimulated DC. Treatment of DC with PL directly induced PKC activity and phosphorylated PTK. Furthermore, CD11b and/or CD18 partially mediated PL-induced DC maturation.
Park
Soon-Kew
SK
Department of Internal Medicine, Pusan National University College of Medicine, Pusan 602-739, Republic of Korea.
Kim
Gi-Young
GY
Lim
Jae-Young
JY
Kwak
Jong-Young
JY
Bae
Yoe-Sik
YS
Lee
Jae-Dong
JD
Oh
Yang-Hyo
YH
Ahn
Soon-Cheol
SC
Park
Yeong-Min
YM
D000818:Animals; D001487:Basidiomycota / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D018664:Interleukin-12 / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D003911:Dextrans; D011134:Polysaccharides; C015219:fluorescein isothiocyanate dextran; D018664:Interleukin-12; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D016650:Fluorescein-5-isothiocyanate