Localization of quinolinic acid in the murine AIDS model of retrovirus-induced immunodeficiency: implications for neurotoxicity and dendritic cell immunopathogenesis.
OBJECTIVE
Using murine AIDS (MAIDS) as a model of retrovirus-induced immunodeficiency, the aims of this study were (1) to determine the cellular source(s) of quinolinic acid (Quin) with regard to its significance as a potential neuroexcitotoxin in AIDS dementia complex, and (2) to characterize the relationship between dendritic cell Quin immunoreactivity and the histopathological changes associated with the progression of disease.


METHODS
Mice with MAIDS were sacrificed from 1 to 16 weeks post-infection. Temporal and spatial changes in the in vivo distribution of Quin at the cellular level were determined by carbodiimide-based immunohistochemical methods.


RESULTS
Cellular Quin immunoreactivity was chronically elevated in lymphoid tissues of mice with MAIDS. In contrast, no cellular Quin immunoreactivity was visible in the brain parenchyma at any timepoint studied.


CONCLUSIONS
These findings are consistent with the view that select immune cells in the peripheral lymphoid tissues may be the primary source of Quin, which may contribute to neurotoxic complications in retrovirus-induced immunodeficiency syndromes. The predominant Quin immunoreactive cell types changed with the progression of disease. A significant finding was the marked increase in the number of Quin immunoreactive dendritic cells in the early phase of MAIDS, suggesting a relationship between dendritic cells and Quin in retroviral infection.
Espey
M G
MG
Department of Biology, Georgetown University, Washington, DC USA.
Tang
Y
Y
Morse
H C
HC
Moffett
J R
JR
Namboodiri
M A
MA
D015526:AIDS Dementia Complex / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001923:Brain Chemistry; D003713:Dendritic Cells / Q000737:chemistry*; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000737:chemistry; D008198:Lymph Nodes / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017378:Quinolinic Acid / Q000032:analysis*; D013154:Spleen / Q000737:chemistry
D017378:Quinolinic Acid