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Tryptophan availability selectively limits NO‐synthase induction in macrophages
Author(s) -
Chiarugi Alberto,
Rovida Elisabetta,
Dello Sbarba Persio,
Moroni Flavio
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0502220
Subject(s) - biology , kynurenine , tumor necrosis factor alpha , nitric oxide synthase , macrophage , nitric oxide , tryptophan , immune system , interferon gamma , incubation , catabolism , cytokine , kynurenine pathway , biochemistry , enzyme , microbiology and biotechnology , in vitro , endocrinology , immunology , amino acid
We studied the effects of tryptophan (TRP) availability on the synthesis and release of nitric oxide (NO) and tumor necrosis factor α (TNF‐α) in interferon‐γ (IFN‐γ)‐activated murine macrophages of the BAC1.2F5 cell line. IFN‐γ (100 U/ml) not only increased the synthesis and release of NO and TNF‐α 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‐γ effects. In TRP‐“starved” cultures, in fact, the IFN‐γ‐mediated NO synthase induction was significantly reduced, and the increased TNF‐α synthesis and release were not affected. Our results suggest hat a reduced local TRP availability may modify macrophage function and possibly the outcome of immune responses.