This article may have a peachy keen reference trail.
Heyes MP. Achim CL. Wiley CA. Major EO. Saito K. Markey SP.
HUMAN MICROGLIA CONVERT L-TRYPTOPHAN INTO THE NEUROTOXIN QUINOLINIC ACID
Biochem J 320(Part 2):595-597 1996
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 [C-13(6)]L-tryptophan in the absence or presence of
interferon gamma. [C-13(6)]Quinolinic acid was identified and quantified
by gas chromatography and electron-capture negative-chemical ionization
mass spectrometry. Both L-kynurenine and [C-13(6)]quinolinic acid were
produced by unstimulated cultures of microglia and macrophages. Interferon
gamma, an inducer of indoleamine 2,3-dioxygenase, increased the
accumulation of L-kynurenine by all three cell types (to more than 40 mu
M). Whereas large quantities of [C-13(6)]quinolinic acid were produced by
microglia and macrophages (to 438 and 1410 nM respectively), minute
quantities of [C-13(6)]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...
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