PMID- 15650060
OWN - NLM
STAT- MEDLINE
DCOM- 20050607
LR  - 20210206
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 105
IP  - 9
DP  - 2005 May 1
TI  - Fc receptor gamma-chain activation via hOSCAR induces survival and maturation of 
      dendritic cells and modulates Toll-like receptor responses.
PG  - 3623-32
AB  - We previously reported the characterization of human osteoclast-associated 
      receptor (hOSCAR), a novel Fc receptor gamma-chain (FcRgamma)-associated receptor 
      expressed by myeloid cells. Here we show that ligation of hOSCAR by specific 
      antibodies promotes dendritic cell (DC) survival by an extracellular 
      signal-regulated kinase (ERK)- and phosphatidylinositol 3-kinase (PI3K)-dependent 
      pathway, linked to expression of the Bcl-2 and Bcl-x(L) antiapoptotic molecules. 
      Crosslinking of hOSCAR leads to maturation of DCs, as demonstrated by 
      up-regulation of maturation markers, decrease in dextran uptake capacity, and 
      secretion of immunesystem effectors such as interleukin-8 (IL-8)/CXC chemokine 
      ligand 8 (CXCL8), IL-12 p40, monocyte chemoattractant protein-1 (MCP-1)/chemokine 
      receptor ligand 2 (CCL2) and macrophage-derived chemokine (MDC)/CCL22. 
      Stimulation of hOSCAR acts in conjunction with the Toll-like receptor (TLR) 
      ligands, lipopolysaccharide (LPS), R-848, and polyinosinic-polycytidylic acid 
      (poly(I:C)), to increase the expression of maturation markers, and to modulate 
      cytokine release. A PI3K-dependent up-regulation of IL-10 release is observed 
      with all the TLR ligands used, whereas regulation of IL-12 production is variable 
      depending on the TLR stimulated. hOSCAR engagement on DCs did not significantly 
      increase the proliferation of naive T cells; however, when co-incubated with TLR 
      ligands, an enhanced proliferation was observed. The percentage of interferon 
      (IFN)-gamma-producing T cells is decreased when hOSCAR engagement is combined 
      with LPS stimulation. Altogether, these data suggest that hOSCAR may modulate the 
      responses of both innate resistance and adaptive immunity.
FAU - Merck, Estelle
AU  - Merck E
AD  - Laboratory for Immunological Research, Schering-Plough, 27 chemin des peupliers, 
      BP11, 69571 Dardilly cedex, France.
FAU - de Saint-Vis, Blandine
AU  - de Saint-Vis B
FAU - Scuiller, Mathieu
AU  - Scuiller M
FAU - Gaillard, Claude
AU  - Gaillard C
FAU - Caux, Christophe
AU  - Caux C
FAU - Trinchieri, Giorgio
AU  - Trinchieri G
FAU - Bates, Elizabeth E M
AU  - Bates EE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050113
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (BCL2L1 protein, human)
RN  - 0 (Cytokines)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (OSCAR protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Receptors, IgG)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Antibodies, Monoclonal
MH  - Cell Differentiation
MH  - Cell Proliferation/drug effects
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/cytology/*immunology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Membrane Glycoproteins/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-bcl-2/biosynthesis
MH  - Receptors, Cell Surface/*metabolism
MH  - Receptors, IgG/*immunology/metabolism
MH  - T-Lymphocytes/cytology/immunology
MH  - Toll-Like Receptors
MH  - bcl-X Protein
EDAT- 2005/01/15 09:00
MHDA- 2005/06/09 09:00
CRDT- 2005/01/15 09:00
PHST- 2005/01/15 09:00 [pubmed]
PHST- 2005/06/09 09:00 [medline]
PHST- 2005/01/15 09:00 [entrez]
AID - S0006-4971(20)45558-2 [pii]
AID - 10.1182/blood-2004-07-2809 [doi]
PST - ppublish
SO  - Blood. 2005 May 1;105(9):3623-32. doi: 10.1182/blood-2004-07-2809. Epub 2005 Jan 
      13.