Document 0587
 DOCN  M94A0587
 TI    Greater quinolinic acid production by macrophages infected with demented
       versus non-demented isolates of HIV.
 DT    9412
 AU    Brew BJ; Pemberton L; Evans L; Heves M; Centre for Immunology, St
       Vincent's Hospital, Sydney, Australia.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:93 (poster no. 37).
       Unique Identifier : AIDSLINE ASHM5/94349068
 AB    OBJECTIVES: We have previously reported that Quinolinic acid (QUIN), a
       neurotoxin acting through the N Methyl D Aspartate receptor, is markedly
       elevated in the cerebrospinal fluid (CSF) of patients with AIDS dementia
       complex (ADC) and is produced by HIV-1 infected and gamma interferon
       stimulated macrophages. We sought to address the following hypotheses:
       i) that HIV infected macrophages produce QUIN not through HIV infection
       per se but through the concomitant production of cytokines such as
       tumour necrosis factor (TNF) and possibly gpl20, ii) that isolates of
       HIV-I from demented patients produce more QUIN than from non-demented
       patients. METHODS: Human macrophages were isolated from peripheral blood
       mononuclear cells by glass adherence and grown in monomed and then AIMV.
       In the first experiment two different concentrations of TNF (0.1 ng/ml
       and 1 ng/ml) were added to the cells and production of QUIN was assessed
       at 0, 24, 36, 48 and 60 hours. In a separate experiment two different
       concentrations of gpl20 (0.1 mcg/ml and 1 mcg/ml) were added to the
       macrophages and QUIN production was assessed at the same time points. To
       test the second hypothesis production of QUIN by macrophages infected
       with isolates taken from patients with ADC stage O and ADC stage 3 was
       undertaken. These isolates had been previously characterised as being
       macrophage tropic or non macrophage tropic according to amount of p24
       that was detected in the supernatants over a 30 day period. Equal
       numbers of macrophages were used for this experiment and cell death was
       quantified at each time point for QUIN analysis by the MTT assay. The
       TCID50 of the viral inoculum was the same for each experiment. To
       substantiate that QUIN was produced by the kynurenine pathway,
       [13C6]-tryptophan was added to the media for each of the latter
       experiments. RESULTS: Macrophages stimulated by TNF produced small
       amounts of QUIN whereas gpl20 stimulated macrophages did not produce
       QUIN. Macrophages infected with demented isolates produced more QUIN
       than those infected with non-demented isolates and the increased
       production related to whether macrophage tropic or non macrophage tropic
       isolates were used: macrophage tropic isolates produced significantly
       more QUIN. CONCLUSIONS: Macrophage production of QUIN is only marginally
       dependent on TNF and independent of gpl20. Other as yet undefined
       factors are responsible for macrophage production of QUIN. The finding
       of greater QUIN production by macrophages infected with isolates from
       demented patients further supports a role for QUIN in the pathogenesis
       of ADC.
 DE    AIDS Dementia Complex/*IMMUNOLOGY  Human  HIV Envelope Protein
       gp120/IMMUNOLOGY  HIV Infections/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY
       Interferon Type II/PHYSIOLOGY  Macrophages/*IMMUNOLOGY  Quinolinic
       Acid/*CEREBROSPINAL FLUID  Tumor Necrosis Factor/PHYSIOLOGY  MEETING
       ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).