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 language | English |
|---|---|
| Pages (from-to) | 633-635 |
| Number of pages | 3 |
| Journal | Biochemical Journal |
| Volume | 283 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-01-1992 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid. / Heyes, M. P.; Saito, K.; Markey, S. P.
In: Biochemical Journal, Vol. 283, No. 3, 01.01.1992, p. 633-635.Research output: Contribution to journal › Article
TY - JOUR
T1 - Human macrophages convert L-tryptophan into the neurotoxin quinolinic acid
AU - Heyes, M. P.
AU - Saito, K.
AU - Markey, S. P.
PY - 1992/1/1
Y1 - 1992/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0026507973&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026507973&partnerID=8YFLogxK
U2 - 10.1042/bj2830633
DO - 10.1042/bj2830633
M3 - Article
C2 - 1534219
AN - SCOPUS:0026507973
VL - 283
SP - 633
EP - 635
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 3
ER -