Submitted October 17, 2008
Accepted March 25, 2009
Ligand of scavenger receptor class-A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-
Jun-O Jin, Hae-Young Park, Qi Xu, Joo-In Park, Tatyana Zvyagintseva, Valentin A. Stonik, and Jong-Young Kwak*
Department of Biochemistry, School of Medicine, Dong-A University, Busan, Korea, Republic of
Medical Research Center for Cancer Molecular Therapy, Dong-A University, Busan, Korea, Republic of
Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian Academy of Sciences, Vladivostok, Russian Federation
* Corresponding author; email: jykwak{at}dau.ac.kr.
Dendritic cells (DCs) are the most potent antigen-presenting cells for naïve 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 MHC-II on the CD11chighCD123low myeloid subset of PBDCs. Furthermore, fucoidan-treated PBDCs produced tumor necrosis factor (TNF)-
but not IL-12p70. Additionally, fucoidan-induced maturation was eliminated by pretreatment with TNF- neutralizing antibody. Finally, interferon-
secretion and T cell proliferation were enhanced by co-culture of T cells with fucoidan-matured PBDCs. Specific inhibitors of p38 MAPK and glycogen synthase kinase 3 suppressed TNF- production and maturation of fucoidan-treated PBDCs. Moreover, MDDCs lacking SR-A failed to up-regulate CD83 expression, TNF- production, and the phosphorylation of p38 MAPK and glycogen synthase kinase 3-
in the presence of fucoidan. Taken together, these results suggest that ligation of SR-A leads to induction of TNF-, which subsequently induces PBDC maturation, thereby leading to enhanced T cell stimulatory capacity.
