Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-alpha.
Dendritic cells (DCs) are the most potent antigen-presenting cells for naive T cells. In this study, scavenger receptor class A type I and type II (SR-A) were shown to be expressed by peripheral blood DCs (PBDCs) and monocyte-derived DCs (MDDCs). In addition, the binding of anti-SR-A antibody to these cells was lower in the presence of fucoidan, an SR-A agonist. Treatment of these DCs with fucoidan or anti-SR-A antibody markedly increased the surface expression of costimulatory molecules CD83 and major histocompatibility complex class II on the CD11c(high)CD123(low) myeloid subset of PBDCs. Furthermore, fucoidan-treated PBDCs produced tumor necrosis factor-alpha (TNF-alpha) but not IL-12p70. In addition, fucoidan-induced maturation was eliminated by pretreatment with TNF-alpha-neutralizing antibody. Finally, interferon-gamma secretion and T-cell proliferation were enhanced by coculture of T cells with fucoidan-matured PBDCs. Specific inhibitors of p38 MAPK and glycogen synthase kinase 3 suppressed TNF-alpha production and maturation of fucoidan-treated PBDCs. Moreover, MDDCs lacking SR-A failed to up-regulate CD83 expression, TNF-alpha production, and phosphorylation of p38 MAPK and glycogen synthase kinase 3-beta in the presence of fucoidan. Taken together, these results suggest that ligation of SR-A leads to induction of TNF-alpha, which subsequently induces PBDC maturation, thereby leading to enhanced T-cell stimulatory capacity.
Jin
Jun-O
JO
Department of Biochemistry, School of Medicine, Dong-A University, Busan, Korea.
Park
Hae-Young
HY
Xu
Qi
Q
Park
Joo-In
JI
Zvyagintseva
Tatyana
T
Stonik
Valentin A
VA
Kwak
Jong-Young
JY
D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006801:Humans; D008024:Ligands; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034622:RNA Interference; D051117:Scavenger Receptors, Class A / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008024:Ligands; D051117:Scavenger Receptors, Class A; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3