Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid

M. P. Heyes, K. Saito, S. P. Markey

Research output: Contribution to journalArticle

199 Citations (Scopus)

Abstract

Substantial increases in the concentrations of the excitotoxin and N-methyl-D-aspartate-receptor agonist quinolinic acid (QUIN) occur in human patients and non-human primates with inflammatory diseases. Such increases were postulated to be secondary to induction of indoleamine 2,3-dioxygenase in inflammatory cells particularly macrophages by interferon-γ. To test this hypothesis human peripheral-blood macrophages were incubated with L-[13C6] tryptophan in the absence or presence of interferon-γ. [13C6]QUIN was quantified by gas chromatography and electron-capture negative-chemical-ionization mass spectrometry. [13C6]QUIN was detected in the incubation medium of both unstimulated and stimulated cultures. Exposure to interferon-γ substantially increased the accumulation of [13C6]QUIN in a dose- and time-dependent manner. The QUIN concentrations achieved exceeded those reported in both cerebrospinal fluid and blood of patients and of non-human primates with inflammatory diseases. Macrophages stimulated with interferon-γ may be an important source of accelerated L-tryptophan conversion into QUIN in inflammatory diseases.

Original languageEnglish
Pages (from-to)633-635
Number of pages3
JournalBiochemical Journal
Volume283
Issue number3
DOIs
Publication statusPublished - 01-01-1992
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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