Immunocytochemical localization of the endogenous neuroexcitotoxin quinolinate in human peripheral blood monocytes/macrophages and the effect of human T-cell lymphotropic virus type I infection.
Quinolinate (Quin), a metabolite in the kynurenine pathway of tryptophan degradation and a neurotoxin that appears to act through the N-methyl-D-aspartate receptor system, was localized in cultured human peripheral blood monocytes/macrophages (PBMOs) by using a recently developed immunocytochemical method. Quin immunoreactivity (Quin-IR) was increased in gamma interferon (IFN-gamma)-stimulated monocytes/macrophages (MOs). In addition, the precursors, tryptophan and kynurenine, significantly increased Quin-IR. Infection of MOs by human T-cell lymphotropic virus type I (HTLV-I) in vitro substantially increased both the number of Quin-IR cells and the intensity of Quin-IR. At the peak of the Quin-IR response, about 40% of the cells were Quin-IR positive. In contrast, only about 2-5% of the cells were positive for HTLV-I, as detected by both immunofluorescence for the HTLV-I antigens and PCR techniques for the HTLV-I Tax gene. These results suggest that HTLV-I-induced Quin production in MOs occurs by an indirect mechanism, perhaps via cytokines produced by the infection but not directly by the virus infection per se. The significance of these findings to the neuropathology of HTLV-I infection is discussed.
Venkateshan
C N
CN
Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Narayanan
R
R
Espey
M G
MG
Moffett
J R
JR
Gajdusek
D C
DC
Gibbs
C J
CJ
Namboodiri
M A
MA
D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007737:Kynurenine / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure / Q000821:virology; D015213:Neuroimmunomodulation; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics / Q000302:isolation & purification; D017378:Quinolinic Acid / Q000097:blood*; D014364:Tryptophan / Q000378:metabolism
D004279:DNA, Viral; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan; D017378:Quinolinic Acid