PMID- 20421643
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20131121
IS  - 1550-6606 (Electronic)
IS  - 0022-1767 (Linking)
VI  - 184
IP  - 11
DP  - 2010 Jun 1
TI  - Neuronal nitric oxide synthase modulates maturation of human dendritic cells.
PG  - 6025-34
LID - 10.4049/jimmunol.0901327 [doi]
AB  - Dendritic cells (DCs) are the most potent APCs of the immune system. 
      Understanding the intercellular and intracellular signaling processes that lead 
      to DC maturation is critical for determining how these cells initiate T 
      cell-mediated immune processes. NO synthesized by the inducible NO synthase 
      (iNOS) is important for the function of murine DCs. In our study, we investigated 
      the regulation of the arginine/NO-system in human monocyte-derived DCs. 
      Maturation of DCs induced by inflammatory cytokines (IL-1beta, TNF, IL-6, and 
      PGE(2)) resulted in a pronounced expression of neuronal NOS (nNOS) but only 
      minimal levels of iNOS and endothelial NOS were detected in human mature DCs. In 
      addition, reporter cell assays revealed the production of NO by mature DCs. 
      Specific inhibitors of NOS (N-nitro-L-arginine methyl ester) or of the NO target 
      guanylyl cyclase (H-(1,2,4)-oxadiazolo [4,3-a] quinoxalin-1-one) prevented DC 
      maturation (shown by decreased expression of MHC class II, costimulatory and CD83 
      molecules and reduced IL-12 production) and preserved an immature phenotype, 
      indicating an autocrine effect of nNOS-derived NO on human DC maturation. 
      Notably, inhibitor-treated DCs were incapable of inducing efficient T cell 
      responses after primary culture and generated an anergic T cell phenotype. In 
      conclusion, our results suggest that, in the human system, nNOS-, but not 
      iNOS-derived NO, plays an important regulatory role for the maturation of DCs 
      and, thus, the induction of pronounced T cell responses.
FAU - Adler, Henric S
AU  - Adler HS
AD  - Department of Dermatology, University of Wurzburg, Wurzburg, Germany.
FAU - Simon, Alexandra
AU  - Simon A
FAU - Graulich, Edith
AU  - Graulich E
FAU - Habermeier, Alice
AU  - Habermeier A
FAU - Bacher, Nicole
AU  - Bacher N
FAU - Friebe, Andreas
AU  - Friebe A
FAU - Closs, Ellen I
AU  - Closs EI
FAU - Steinbrink, Kerstin
AU  - Steinbrink K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100426
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
SB  - IM
MH  - Cell Differentiation/*immunology
MH  - Cell Line
MH  - Cell Separation
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*cytology/immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoblotting
MH  - Lymphocyte Activation/immunology
MH  - Nitric Oxide/biosynthesis/metabolism
MH  - Nitric Oxide Synthase Type I/*immunology/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2010/04/28 06:00
MHDA- 2010/06/15 06:00
CRDT- 2010/04/28 06:00
PHST- 2010/04/28 06:00 [entrez]
PHST- 2010/04/28 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
AID - jimmunol.0901327 [pii]
AID - 10.4049/jimmunol.0901327 [doi]
PST - ppublish
SO  - J Immunol. 2010 Jun 1;184(11):6025-34. doi: 10.4049/jimmunol.0901327. Epub 2010 
      Apr 26.