Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs.

Quinolinate is a tryptophan metabolite and an intermediary in nicotinamide adenine dinucleotide (NAD+) synthesis in hepatocytes. Kynurenine is an upstream metabolite in the same biochemical pathway. Under normal physiological conditions, kynurenine is thought to be produced primarily in the liver as an NAD+ precursor. However, during immune stimulation or inflammation, numerous extrahepatic tissues convert systemic tryptophan to kynurenine, and its concentration subsequently rises dramatically in blood. The fate and role of extrahepatic kynurenine are uncertain. In order to begin addressing this question, the present study was performed to determine which cell types can produce quinolinate from either systemic tryptophan or kynurenine. By using highly specific antibodies to protein-coupled quinolinate, we found that intraperitoneal injections of tryptophan led to increased quinolinate immunoreactivity primarily in hepatocytes, with moderate increases in tissue macrophages 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 thymic medulla. These findings suggest that hepatocytes do not make significant use of extracellular kynurenine for quinolinate or NAD+ synthesis, and that, instead, extrahepatic kynurenine is preferentially metabolized by immune cells throughout the body. The possible significance of the preferential metabolism of kynurenine by immune cells during an immune response is discussed.

In situ expression of fibroblast growth factor receptors by oligodendrocyte progenitors and oligodendrocytes in adult mouse central nervous system.

Basic fibroblast growth factor (bFGF) induces proliferation and alters differentiation of cultured oligodendrocyte lineage cells. In situ, bFGF is present in normal adult central nervous system (CNS) and upregulated during an early stage of various pathological conditions. We examined the expression of receptors for bFGF (FGFRs) by oligodendrocyte progenitors and oligodendrocytes in situ in normal adult mouse CNS to further understand the potential in situ response to bFGF. We found FGFR immunoreactivity in oligodendrocyte progenitors, identified by expression of NG2 or platelet-derived growth factor alpha receptor (PDGFalphaR), and in oligodendrocytes expressing 2',3'-cyclic nucleotide 3' phosphodiesterase. Particularly interesting is the demonstration that oligodendrocyte progenitors simultaneously expressing receptors for both bFGF and PDGF-AA are present in normal adult CNS. Since in vitro bFGF and PDGF-AA in combination induce oligodendrocyte progenitors from normal adult CNS to undergo rapid proliferation and migration, the in situ coexpression of FGFRs and PDGFalphaR supports the hypothesis that oligodendrocyte progenitors can respond to bFGF and PDGF-AA in situ, and that both growth factors may be critical for repopulation of demyelinated lesions during remyelination.