Infection of macrophages (M/M) by human immunodeficiency virus (HIV) is a main pathogenetic event leading to neuronal dysfunction and death in patients with AIDS dementia complex. Alteration of viability of neurons and astrocytes occurs in vivo even without their infection, thus it is conceivable that HIV-infected M/M may affect viability of such cells even without direct infection. To assess this hypothesis, we studied the effects of HIV-infected M/M on an astrocytic cell-line lacking CD4-receptor expression. Exposure to supernatants of HIV-infected M/M triggers complete disruption and apoptotic death of astrocytic cells. This effect is not related to HIV transmission from infected M/M, because HIV-DNA and p24 production in astrocytic cells remained negative. Apoptotic death of astrocytes is mainly mediated by Fas ligand released in supernatants of HIV-infected M/M (as demonstrated by complete reversal of such phenomenon by adding neutralizing antibodies against CD95 receptor). Treatment of astrocytic cells with recombinant (biologically active) Tat induces < 10% apoptosis, and gp120 was totally ineffective. Treatment of HIV-infected M/M with AZT completely reverses the proapoptotic effect of their supernatants on astrocytes, thus demonstrating that productive virus replication within M/M is required for the induction of astrocytic cell death. Taken together, data suggest that homeostasis of astrocytes may be affected by HIV-infected M/M in the absence of productive infection of target cells. This phenomenon may help to explain the cellular damage found in HIV-infected patients also in areas of the brain not strictly adjacent to HIV-infected M/M.

Aquaro, S., Panti, S., Caroleo, M., Balestra, E., Cenci, A., Forbici, F., et al. (2000). Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. JOURNAL OF LEUKOCYTE BIOLOGY, 68(3), 429-435.

Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes

AQUARO, STEFANO;BALESTRA, EMANUELA;TESTI, ROBERTO;MOLLACE, VINCENZO;PERNO, CARLO FEDERICO
2000-09-01

Abstract

Infection of macrophages (M/M) by human immunodeficiency virus (HIV) is a main pathogenetic event leading to neuronal dysfunction and death in patients with AIDS dementia complex. Alteration of viability of neurons and astrocytes occurs in vivo even without their infection, thus it is conceivable that HIV-infected M/M may affect viability of such cells even without direct infection. To assess this hypothesis, we studied the effects of HIV-infected M/M on an astrocytic cell-line lacking CD4-receptor expression. Exposure to supernatants of HIV-infected M/M triggers complete disruption and apoptotic death of astrocytic cells. This effect is not related to HIV transmission from infected M/M, because HIV-DNA and p24 production in astrocytic cells remained negative. Apoptotic death of astrocytes is mainly mediated by Fas ligand released in supernatants of HIV-infected M/M (as demonstrated by complete reversal of such phenomenon by adding neutralizing antibodies against CD95 receptor). Treatment of astrocytic cells with recombinant (biologically active) Tat induces < 10% apoptosis, and gp120 was totally ineffective. Treatment of HIV-infected M/M with AZT completely reverses the proapoptotic effect of their supernatants on astrocytes, thus demonstrating that productive virus replication within M/M is required for the induction of astrocytic cell death. Taken together, data suggest that homeostasis of astrocytes may be affected by HIV-infected M/M in the absence of productive infection of target cells. This phenomenon may help to explain the cellular damage found in HIV-infected patients also in areas of the brain not strictly adjacent to HIV-infected M/M.
set-2000
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/04 - PATOLOGIA GENERALE
English
Macrophages; Anti-HIV Agents; Apoptosis; Membrane Glycoproteins; Astrocytes; Humans; Zidovudine; Antigens, CD95; Homeostasis; Gene Products, tat; Necrosis; HIV Envelope Protein gp120; Cells, Cultured; tat Gene Products, Human Immunodeficiency Virus; Fas Ligand Protein; Cell Communication; Middle Aged; HIV; Male
Aquaro, S., Panti, S., Caroleo, M., Balestra, E., Cenci, A., Forbici, F., et al. (2000). Primary macrophages infected by human immunodeficiency virus trigger CD95-mediated apoptosis of uninfected astrocytes. JOURNAL OF LEUKOCYTE BIOLOGY, 68(3), 429-435.
Aquaro, S; Panti, S; Caroleo, M; Balestra, E; Cenci, A; Forbici, F; Ippolito, G; Mastino, A; Testi, R; Mollace, V; Caliò, R; Perno, Cf
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/62740
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