M-CSF production by HIV-1-infected monocytes and its intrathecal synthesis. Implications for neurological HIV-1-related disease.
Macrophage-colony stimulating factor (M-CSF) is detectable in the cerebrospinal fluid (SF) of HIV-1-infected patients, and may be produced intrathecally by both reactive astrocytes and cells of the monocyte/macrophage (MO) lineage, microglial cells included. Since MO constitute the target cells for HIV-1 in the central nervous system (CNS), the culture conditions that induce M-CSF production by HIV-1-infected MO were studied. MO cultures infected with supernatants (SN) of HIV-1-infected peripheral blood lymphocyte (PBL) cultures produced only trace or undetectable amounts of M-CSF. Co-cultures of MO with normal PBL released high amounts of M-CSF, suggesting that viable cell-to-cell interactions are required to induce cytokine production by MO and/or PBL. M-CSF production was markedly increased in the MO co-cultured with HIV-1-infected PBL, thus implying that HIV-1 induces increased cytokine synthesis/release by MO and/or PBL only when cell membrane-associated messages are operating. Intracerebrally synthesized M-CSF by HIV-1-infected MO may play a role in promoting viral replication/spread within the CNS, and inducing brain damage by stimulating microglia proliferation, and neurotoxic factor release by these cells.
Gallo
P
P
Institute of Neurology, University of Padua, School of Medicine, Italy.
De Rossi
A
A
Sivieri
S
S
Chieco-Bianchi
L
L
Tavolato
B
B
D016263:AIDS-Associated Nephropathy / Q000209:etiology*; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D015497:HIV-1; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism* / Q000382:microbiology
D016173:Macrophage Colony-Stimulating Factor