Monocyte-derived dendritic cells release neopterin.
Increased neopterin concentrations in body fluids are found in diseases associated with activated, cell-mediated immunity including infections, autoimmune diseases, and certain malignancies. Monocytes/macrophages are known to secrete large amounts of neopterin upon stimulation with interferon-gamma (IFN-gamma). Ontogenetically, the major part of dendritic cells (DC) belongs to the myeloid lineage. Therefore, we investigated whether cultured monocyte-derived DC can elaborate neopterin. Cells were treated with cytokines in the presence or absence of monocyte-conditioned medium as a maturation stimulus. DC secreted an average 3.5 nmol/l neopterin. In response to IFN-gamma, cells significantly increased their output of neopterin. In distinction to monocytes/macrophages, neopterin production in DC was highly sensitive to IFN-alpha and IFN-beta. Further, lipopolysaccharides (LPS) enhanced neopterin synthesis, whereas tumor necrosis factor alpha, interleukin (IL)-1beta, IL-2, IL-10, and IL-18 were ineffective. Simultaneously, tryptophan degradation by induction of indoleamine (2,3)-dioxygenase (IDO) was tested in stimulated cells. Our results showed that IFN-gamma as well as LPS are inducers of IDO in DC.
Wirleitner
Barbara
B
Institute for Medical Chemistry and Biochemistry, University of Innsbruck, Austria.
Reider
Daniela
D
Ebner
Susanne
S
Böck
Günther
G
Widner
Bernhard
B
Jaeger
Matthias
M
Schennach
Harald
H
Romani
Nikolaus
N
Fuchs
Dietmar
D
D018929:Cell Culture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology*; D019798:Neopterin / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000096:biosynthesis / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D014443:Tyrosine; D019798:Neopterin; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase