Gliotoxicity, reverse transcriptase activity and retroviral RNA in monocyte/macrophage culture supernatants from patients with multiple sclerosis.
In investigating a possible link between a novel retroviral agent (provisionally called MSRV), recently characterised in multiple sclerosis (MS), and the neuropathology of MS, it was found that there was a significant correlation between gliotoxicity and reverse transcriptase activity in monocyte/macrophage culture supernatants (MMCS) unique to MS patients. MMCS from healthy controls and patients with other neurological diseases did not display either gliotoxicity or reverse transcriptase activity. The observed gliotoxic effect was an initial, intermediate filament network disorganization and subsequent cell death which was specific to astrocytes and oligodendrocytes. The reverse transcriptase activity and MSRV-specific RNA were observed during the first 2 weeks of culture in MMCS from patients with active MS. The further elucidation of the molecular form(s) of this gliotoxic factor and its original source may be crucial in elucidating important etiopathogenic mechanisms in MS.
Ménard
A
A
INSERM, Laboratoire de Neuromodulations Interactives et Neuropathologies, Paris, France.
Amouri
R
R
Michel
M
M
Marcel
F
F
Brouillet
A
A
Belliveau
J
J
Geny
C
C
Deforges
L
L
Malcus-Vocanson
C
C
Armstrong
M
M
Lyon-Caen
O
O
Mandrand
B
B
Dobránsky
T
T
Rieger
F
F
Perron
H
H
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000473:pathology; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003470:Culture Media; D005333:Fetus; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000473:pathology* / Q000821:virology; D009000:Monocytes / Q000166:cytology / Q000473:pathology* / Q000821:virology; D009103:Multiple Sclerosis / Q000097:blood* / Q000821:virology*; D009498:Neurotoxins / Q000302:isolation & purification* / Q000633:toxicity; D009836:Oligodendroglia / Q000166:cytology / Q000473:pathology; D011506:Proteins / Q000302:isolation & purification / Q000633:toxicity; D012367:RNA, Viral / Q000302:isolation & purification*; D012194:RNA-Directed DNA Polymerase / Q000302:isolation & purification*; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000201:enzymology / Q000235:genetics / Q000302:isolation & purification*
D003470:Culture Media; D009498:Neurotoxins; D011506:Proteins; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase