PMID- 19351958 OWN - NLM STAT- MEDLINE DCOM- 20090727 LR - 20240109 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 113 IP - 23 DP - 2009 Jun 4 TI - Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-alpha. PG - 5839-47 LID - 10.1182/blood-2008-10-184796 [doi] AB - 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. FAU - Jin, Jun-O AU - Jin JO AD - Department of Biochemistry, School of Medicine, Dong-A University, Busan, Korea. FAU - Park, Hae-Young AU - Park HY FAU - Xu, Qi AU - Xu Q FAU - Park, Joo-In AU - Park JI FAU - Zvyagintseva, Tatyana AU - Zvyagintseva T FAU - Stonik, Valentin A AU - Stonik VA FAU - Kwak, Jong-Young AU - Kwak JY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090407 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Ligands) RN - 0 (Scavenger Receptors, Class A) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) SB - IM MH - Cell Differentiation/*immunology MH - Cell Proliferation MH - Cells, Cultured MH - Dendritic Cells/*cytology/*immunology/metabolism MH - Glycogen Synthase Kinase 3/metabolism MH - Humans MH - Ligands MH - Phosphatidylinositol 3-Kinases/metabolism MH - RNA Interference MH - Scavenger Receptors, Class A/classification/genetics/*immunology/metabolism MH - Tumor Necrosis Factor-alpha/*biosynthesis MH - p38 Mitogen-Activated Protein Kinases/metabolism EDAT- 2009/04/09 09:00 MHDA- 2009/07/28 09:00 CRDT- 2009/04/09 09:00 PHST- 2009/04/09 09:00 [entrez] PHST- 2009/04/09 09:00 [pubmed] PHST- 2009/07/28 09:00 [medline] AID - S0006-4971(20)37339-0 [pii] AID - 10.1182/blood-2008-10-184796 [doi] PST - ppublish SO - Blood. 2009 Jun 4;113(23):5839-47. doi: 10.1182/blood-2008-10-184796. Epub 2009 Apr 7.