DIFFERENTIAL-EFFECTS OF KYNURENINE AND TRYPTOPHAN TREATMENT ON QUINOLINATE IMMUNOREACTIVITY IN RAT LYMPHOID AND NONLYMPHOID ORGANS

Quinolinate is a tryptophan metabolite and an intermediary in nicotina mide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under norma l physiological conditions, kynurenine is thought to be produced prima rily in the liver as an NAD+ precursor. However, during immune stimula tion or inflammation, numerous extrahepatic tissues convert systemic t ryptophan to kynurenine, and its concentration subsequently rises dram atically in blood. The fate and role of extrahepatic kynurenine are un certain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate f rom either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperiton eal injections of tryptophan led to increased quinolinate immunoreacti vity primarily in hepatocytes, with moderate increases in tissue macro phages and splenic follicles. In contrast, intraperitoneal injections of kynurenine did not result in any significant increase in hepatocyte quinolinate immunoreactivity, but rather led to dramatic increases in immunoreactivity in tissue macrophages, splenic white pulp, and thymi c medulla. These findings suggest that hepatocytes do not make signifi cant use of extracellular kynurenine for quinolinate or NAD+ synthesis , and that, instead, extrahepatic kynurenine is preferentially metabol ized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an i mmune response is discussed.