Human microglia convert L-tryptophan into the neurotoxin quinolinic acid

Melvyn P. Heyes, Cristian L. Achim, Clayton A. Wiley, Eugene O. Major, Kuniaki Saito, Sanford P. Markey

Research output: Contribution to journalArticle

242 Citations (Scopus)

Abstract

Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [13C6,]L-tryptophan in the absence or presence of interferon γ. [13C6]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [13C6]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon γ, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 μM). Whereas large quantities of [13C6]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [13C6]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases.

Original languageEnglish
Pages (from-to)595-597
Number of pages3
JournalBiochemical Journal
Volume320
Issue number2
DOIs
Publication statusPublished - 01-12-1996
Externally publishedYes

Fingerprint

Quinolinic Acid
Neurotoxins
Microglia
Tryptophan
Macrophages
Kynurenine
Brain
Neurology
Cell culture
Central Nervous System
Interferon Inducers
Indoleamine-Pyrrole 2,3,-Dioxygenase
Metabolites
Astrocytes
Gas chromatography
Gas Chromatography
Interferons
Neurons
Ionization
Mass spectrometry

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Heyes, M. P., Achim, C. L., Wiley, C. A., Major, E. O., Saito, K., & Markey, S. P. (1996). Human microglia convert L-tryptophan into the neurotoxin quinolinic acid. Biochemical Journal, 320(2), 595-597. https://doi.org/10.1042/bj3200595
Heyes, Melvyn P. ; Achim, Cristian L. ; Wiley, Clayton A. ; Major, Eugene O. ; Saito, Kuniaki ; Markey, Sanford P. / Human microglia convert L-tryptophan into the neurotoxin quinolinic acid. In: Biochemical Journal. 1996 ; Vol. 320, No. 2. pp. 595-597.
@article{2088838c92c14edfbeea540378d3d962,
title = "Human microglia convert L-tryptophan into the neurotoxin quinolinic acid",
abstract = "Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [13C6,]L-tryptophan in the absence or presence of interferon γ. [13C6]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [13C6]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon γ, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 μM). Whereas large quantities of [13C6]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [13C6]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases.",
author = "Heyes, {Melvyn P.} and Achim, {Cristian L.} and Wiley, {Clayton A.} and Major, {Eugene O.} and Kuniaki Saito and Markey, {Sanford P.}",
year = "1996",
month = "12",
day = "1",
doi = "10.1042/bj3200595",
language = "English",
volume = "320",
pages = "595--597",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

Heyes, MP, Achim, CL, Wiley, CA, Major, EO, Saito, K & Markey, SP 1996, 'Human microglia convert L-tryptophan into the neurotoxin quinolinic acid', Biochemical Journal, vol. 320, no. 2, pp. 595-597. https://doi.org/10.1042/bj3200595

Human microglia convert L-tryptophan into the neurotoxin quinolinic acid. / Heyes, Melvyn P.; Achim, Cristian L.; Wiley, Clayton A.; Major, Eugene O.; Saito, Kuniaki; Markey, Sanford P.

In: Biochemical Journal, Vol. 320, No. 2, 01.12.1996, p. 595-597.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Human microglia convert L-tryptophan into the neurotoxin quinolinic acid

AU - Heyes, Melvyn P.

AU - Achim, Cristian L.

AU - Wiley, Clayton A.

AU - Major, Eugene O.

AU - Saito, Kuniaki

AU - Markey, Sanford P.

PY - 1996/12/1

Y1 - 1996/12/1

N2 - Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [13C6,]L-tryptophan in the absence or presence of interferon γ. [13C6]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [13C6]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon γ, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 μM). Whereas large quantities of [13C6]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [13C6]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases.

AB - Immune activation leads to accumulations of the neurotoxin and kynurenine pathway metabolite quinolinic acid within the central nervous system of human patients. Whereas macrophages can convert L-tryptophan to quinolinic acid, it is not known whether human brain microglia can synthesize quinolinic acid. Human microglia, peripheral blood macrophages and cultures of human fetal brain cells (astrocytes and neurons) were incubated with [13C6,]L-tryptophan in the absence or presence of interferon γ. [13C6]Quinolinic acid was identified and quantified by gas chromatography and electron-capture negative-chemical ionization mass spectrometry. Both L-kynurenine and [13C6]quinolinic acid were produced by unstimulated cultures of microglia and macrophages. Interferon γ, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 μM). Whereas large quantities of [13C6]quinolinic acid were produced by microglia and macrophages (to 438 and 1410 nM respectively), minute quantities of [13C6]quinolinic acid were produced in human fetal brain cultures (not more than 2 nM). Activated microglia and macrophage infiltrates into the brain might be an important source of accelerated conversion of L-tryptophan into quinolinic acid within the central nervous system in inflammatory diseases.

UR - http://www.scopus.com/inward/record.url?scp=0029960647&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029960647&partnerID=8YFLogxK

U2 - 10.1042/bj3200595

DO - 10.1042/bj3200595

M3 - Article

C2 - 8973572

AN - SCOPUS:0029960647

VL - 320

SP - 595

EP - 597

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -