Treatment of multiple sclerosis patients with interferon-beta primes monocyte-derived macrophages for apoptotic cell death.
Although interferon (IFN)-beta has shown a significant clinical benefit in multiple sclerosis (MS), its mechanism of action remains unclear. We found that IFN-beta treatment of patients with MS resulted in a significant increase in apoptotic cell death (measured by annexin V staining and nuclear fragmentation) of monocyte-derived macrophages, as compared with cells derived from patients before treatment. Stimulation of the cells with IFN-beta in vitro resulted in an even further increase of annexin V binding, as well as increased Fas (CD 95, APO-1) expression. However, no increased Fas expression, apoptotic monocytes, or monocytopenia were observed upon in vivo treatment. This indicates that IFN-beta does not deliver a death signal to monocytes but rather primes for subsequent macrophage apoptosis upon activation or differentiation.
Van Weyenbergh
J
J
U365 INSERM, Hôpital La Pitié-Salpêtrière, Paris, France. ejomaflo@svn.com.br
Wietzerbin
J
J
Rouillard
D
D
Barral-Netto
M
M
Liblau
R
R
D000328:Adult; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D019070:Cell Lineage; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D016899:Interferon-beta / Q000494:pharmacology / Q000627:therapeutic use*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics
D017304:Annexin A5; D007155:Immunologic Factors; D019014:fas Receptor; D016899:Interferon-beta