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(Journal of Leukocyte Biology. 2002;72:1148-1153.)
© 2002 by Society for Leukocyte Biology

Monocyte-derived dendritic cells release neopterin

Barbara Wirleitner{ddagger}, Daniela Reider*, Susanne Ebner*, Günther Böck{dagger}, Bernhard Widner{ddagger}, Matthias Jaeger{ddagger}, Harald Schennach§, Nikolaus Romani* and Dietmar Fuchs{ddagger},||

Institutes for
{ddagger} Medical Chemistry and Biochemistry, and for
{dagger} Experimental Pathology, University of Innsbruck and
* Department of Dermatology, University of Innsbruck;
§ Central Institute for Blood Transfusion and Immunology, University Hospital, Innsbruck; and
|| Ludwig Boltzmann Institute of AIDS-Research, Innsbrugh, Austria

Correspondence: Dr. Dietmar Fuchs, Institute of Medical Chemistry and Biochemistry, University of Innsbruck, Fritz-Pregl-Strasse 3, A-6020 Innsbruck, Austria. E-mail: Dietmar.Fuchs{at}uibk.ac.at

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-ß. Further, lipopolysaccharides (LPS) enhanced neopterin synthesis, whereas tumor necrosis factor {alpha}, interleukin (IL)-1ß, 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.

Key Words: IFN-{gamma} • pteridines • tryptophan degradation




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