A cytotoxic factor for glial cells: a new avenue of research for multiple sclerosis?
A novel retrovirus, provisionally called Multiple Sclerosis RetroVirus (MSRV), was recently described in multiple sclerosis (MS). We report here that monocyte/macrophage culture supernatants from MS patients containing reverse transcriptase activity secrete a cytotoxin which induces death of primary mouse cortical glial cells. This cytotoxin, which was also found in MS cerebrospinal fluid, specifically causes death of mouse immortalized astrocytes and oligodendrocytes in vitro and seems to be associated to MSRV-specific RNA. This toxic factor, called gliotoxin, is present only in active cases of MS and is a stable glycosylated protein of 17 kDa, in CSF as well as in monocyte/macrophage culture supernatants. Since this gliotoxin is highly toxic for glial cells, it may represent an initial pathogenic factor, leading to the neuropathological features of MS, like blood brain barrier disruption and demyelination.
Ménard
A
A
INSERM, Laboratoire de Neuromodulations Interactives et Neuropathologies, Paris, France.
Paranhos-Baccala
G
G
Pelletier
J
J
Mandrand
B
B
Seigneurin
J M
JM
Perron
H
H
Reiger
F
F
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D002461:Cell Line, Transformed; D002474:Cell-Free System; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003603:Cytotoxins / Q000378:metabolism* / Q000502:physiology; D005333:Fetus; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects; D012194:RNA-Directed DNA Polymerase; D051381:Rats; D017208:Rats, Wistar
D003603:Cytotoxins; D012194:RNA-Directed DNA Polymerase