Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid

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

Research output: Contribution to journalArticle

195 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

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Quinolinic Acid
Macrophages
Neurotoxins
Tryptophan
Interferons
Primates
Blood
Indoleamine-Pyrrole 2,3,-Dioxygenase
Cerebrospinal fluid
N-Methyl-D-Aspartate Receptors
Gas chromatography
Gas Chromatography
Ionization
Mass spectrometry
Cerebrospinal Fluid
Mass Spectrometry
Electrons

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Heyes, M. P. ; Saito, Kuniaki ; Markey, S. P. / Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid. In: Biochemical Journal. 1992 ; Vol. 283, No. 3. pp. 633-635.
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Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid. / Heyes, M. P.; Saito, Kuniaki; Markey, S. P.

In: Biochemical Journal, Vol. 283, No. 3, 01.01.1992, p. 633-635.

Research output: Contribution to journalArticle

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