Quinolinate (Quin) is a classic example of a biochemical double-edged sword, acting as both essential metabolite and potent neurotoxin. Quin is an important metabolite in the kynurenine pathway of tryptophan catabolism leading to the de novo synthesis of nicotinamide adenine dinucleotide (NAD⁺). As a precursor for NAD⁺, Quin can direct a portion of tryptophan catabolism toward replenishing cellular NAD⁺ levels in response to inflammation and infection. Intracellular Quin levels increase dramatically in response to immune stimulation [e.g., lipopolysaccharide (LPS) or pokeweed mitogen (PWM)] in macrophages, microglia, dendritic cells, and other cells of the immune system. NAD⁺ serves numerous functions including energy production, the poly ADP ribose polymerization (PARP) reaction involved in DNA repair, and the activity of various enzymes such as the NAD⁺-dependent deacetylases known as sirtuins. We used highly specific antibodies to protein-coupled Quin to delineate cells that accumulate Quin as a key aspect of the response to immune stimulation and infection. Here, we describe Quin staining in the brain, spleen, and liver after LPS administration to the brain or systemic PWM administration. Quin expression was strong in immune cells in the periphery after both treatments, whereas very limited Quin expression was observed in the brain even after direct LPS injection. Immunoreactive cells exhibited diverse morphology ranging from foam cells to cells with membrane extensions related to cell motility. We also examined protein expression changes in the spleen after kynurenine administration. Acute (8 h) and prolonged (48 h) kynurenine administration led to significant changes in protein expression in the spleen, including multiple changes involved with cytoskeletal rearrangements associated with cell motility. Kynurenine administration resulted in several expression level changes in proteins associated with heat shock protein 90 (HSP90), a chaperone for the aryl-hydrocarbon receptor (AHR), which is the primary kynurenine metabolite receptor. We propose that cells with high levels of Quin are those that are currently releasing kynurenine pathway metabolites as well as accumulating Quin for sustained NAD⁺ synthesis from tryptophan. Further, we propose that the kynurenine pathway may be linked to the regulation of cell motility in immune and cancer cells.

喹啉酸盐（Quin）是生化双刃剑的典型例子，既是必需的代谢物，又是强效的神经毒素。 Quin 是色氨酸分解代谢的犬尿氨酸途径中的重要代谢物，导致烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 从头合成。作为 NAD ⁺的前体，Quin 可以引导部分色氨酸分解代谢来补充细胞 NAD ⁺水平，以应对炎症和感染。巨噬细胞、小胶质细胞、树突状细胞和免疫系统的其他细胞中，细胞内奎因水平响应免疫刺激[例如脂多糖（LPS）或美洲商陆丝裂原（PWM）]而急剧增加。 NAD ⁺具有多种功能，包括能量产生、参与 DNA 修复的聚 ADP 核糖聚合 (PARP) 反应以及各种酶的活性，例如 NAD ⁺依赖性脱乙酰酶（称为 Sirtuins）。我们使用蛋白质偶联奎因的高度特异性抗体来描绘积累奎因的细胞，这是对免疫刺激和感染反应的一个关键方面。在这里，我们描述了向大脑施用 LPS 或全身 PWM 施用后，大脑、脾脏和肝脏中的奎因染色。两种治疗后，外周免疫细胞中的 Quin 表达很强，而即使在直接注射 LPS 后，在大脑中也观察到非常有限的 Quin 表达。免疫反应细胞表现出多种形态，从泡沫细胞到具有与细胞运动相关的膜延伸的细胞。我们还检查了犬尿氨酸给药后脾脏中蛋白质表达的变化。 急性（8小时）和长期（48小时）犬尿氨酸给药导致脾脏中蛋白质表达的显着变化，包括与细胞运动相关的细胞骨架重排有关的多种变化。给予犬尿氨酸会导致与热休克蛋白 90 (HSP90) 相关的蛋白质表达水平发生一些变化，热休克蛋白 90 是芳基烃受体 (AHR) 的伴侣，是主要的犬尿氨酸代谢受体。我们认为具有高水平 Quin 的细胞是那些当前正在释放犬尿氨酸途径代谢物以及积累 Quin 以从色氨酸持续合成 NAD ⁺的细胞。此外，我们提出犬尿氨酸途径可能与免疫细胞和癌细胞中细胞运动的调节有关。