Heyes M P, Achim C L, Wiley C A, Major E O, Saito K, Markey S P
Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, MD 20892, USA.
Biochem J. 1996 Dec 1;320 ( Pt 2)(Pt 2):595-7. doi: 10.1042/bj3200595.
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 gamma. [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 gamma, an inducer of indoleamine 2,3-dioxygenase, increased the accumulation of L-kynurenine by all three cell types (to more than 40 microM). 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.
免疫激活会导致神经毒素和犬尿氨酸途径代谢物喹啉酸在人类患者的中枢神经系统中蓄积。虽然巨噬细胞可将L-色氨酸转化为喹啉酸，但尚不清楚人脑小胶质细胞是否能合成喹啉酸。将人小胶质细胞、外周血巨噬细胞以及人胎脑细胞培养物（星形胶质细胞和神经元）在不存在或存在干扰素γ的情况下与[13C6]L-色氨酸一起孵育。通过气相色谱和电子捕获负化学电离质谱法对[13C6]喹啉酸进行鉴定和定量。未受刺激的小胶质细胞和巨噬细胞培养物均可产生L-犬尿氨酸和[13C6]喹啉酸。吲哚胺2,3-双加氧酶的诱导剂干扰素γ可使所有三种细胞类型的L-犬尿氨酸蓄积增加（超过40 μM）。小胶质细胞和巨噬细胞可产生大量的[13C6]喹啉酸（分别为438和1410 nM），而人胎脑细胞培养物中产生的[13C6]喹啉酸量极少（不超过2 nM）。活化的小胶质细胞和浸润入脑的巨噬细胞可能是炎症性疾病中枢神经系统中L-色氨酸加速转化为喹啉酸的重要来源。
