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(Journal of Leukocyte Biology. 2003;73:172-177.)
© 2003 by Society for Leukocyte Biology

Tryptophan availability selectively limits NO-synthase induction in macrophages

Alberto Chiarugi*, Elisabetta Rovida{dagger}, Persio Dello Sbarba{dagger} and Flavio Moroni*

Departments of
* Preclinical and Clinical Pharmacology and
{dagger} Experimental Pathology and Oncology, University of Florence, Italy

Correspondence: Prof. Flavio Moroni, Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy. E-mail: moronif{at}ds.unifi.it

We studied the effects of tryptophan (TRP) availability on the synthesis and release of nitric oxide (NO) and tumor necrosis factor {alpha} (TNF-{alpha}) in interferon-{gamma} (IFN-{gamma})-activated murine macrophages of the BAC1.2F5 cell line. IFN-{gamma} (100 U/ml) not only increased the synthesis and release of NO and TNF-{alpha} from these cells but also induced indoleamine-2,3-dioxygenase, the rate-limiting enzyme of TRP catabolism. This led to an increased metabolic flow through the kynurenine pathway and significantly decreased TRP levels in macrophage incubation media. Low TRP concentrations in the media, however, modified IFN-{gamma} effects. In TRP-"starved" cultures, in fact, the IFN-{gamma}-mediated NO synthase induction was significantly reduced, and the increased TNF-{alpha} synthesis and release were not affected. Our results suggest that a reduced local TRP availability may modify macrophage function and possibly the outcome of immune responses.

Key Words: nitric oxide • indoleamine-dioxygenase • arginine • nicotinamide




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