Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-α

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Abstract
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 CD11chighCD123low myeloid subset of PBDCs. Furthermore, fucoidan-treated PBDCs produced tumor necrosis factor-α (TNF-α) but not IL-12p70. In addition, fucoidan-induced maturation was eliminated by pretreatment with TNF-α–neutralizing antibody. Finally, interferon-γ 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-α production and maturation of fucoidan-treated PBDCs. Moreover, MDDCs lacking SR-A failed to up-regulate CD83 expression, TNF-α production, and phosphorylation of p38 MAPK and glycogen synthase kinase 3-β in the presence of fucoidan. Taken together, these results suggest that ligation of SR-A leads to induction of TNF-α, which subsequently induces PBDC maturation, thereby leading to enhanced T-cell stimulatory capacity.

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