Involvement of Fas and FasL in Ectromelia virus-induced apoptosis in mouse brain.
In this study we showed that the virulent Moscow strain of Ectromelia virus (ECTV-MOS) infection leads to induction of apoptosis in the BALB/c mouse central nervous system. ECTV-MOS-infected cells and inflammation sites were found in brain parenchyma between 5 and 15 days after footpad infection with ECTV-MOS. Infected cells consisted of microglia and monocytes, astrocytes and oligodendrocytes and these type of cells underwent apoptosis within 5-15 days post infection (d.p.i.). The highest number of apoptotic cells was found at 5 and 10 d.p.i. and represented mainly microglia (61.4% and 38.6% of apoptotic cells, respectively) and astrocytes (21% and 8.9%, respectively). The number of apoptotic oligodendrocytes was 5.4% and 4.5%, respectively. Fluorometric assays demonstrated involvement of caspase-1, -3 and -8 but not caspase-9 in apoptosis in ECTV-MOS-infected mouse brains. Expression of Fas/FasL was significantly increased on ECTV-MOS-infected cells between 5 and 15 d.p.i., whereas Fas was up-regulated also on the surrounding, non-infected cells. Taking together we may conclude that ECTV-MOS infection of microglia and astrocytes leads to local inflammation resulting in Fas/FasL up-regulation and apoptosis, which limits mouse central nervous system infection with ECTV-MOS.
Krzyzowska
Małgorzata
M
Division of Virology, Mycology and Immunology, Department of Preclinical Sciences, Ciszewskiego 8, 02-786 Warsaw, Poland. krzyzowska@yahoo.com
Cymerys
Joanna
J
Winnicka
Anna
A
Niemiałtowski
Marek
M
D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000473:pathology / Q000821:virology; D001921:Brain / Q000473:pathology* / Q000821:virology*; D020169:Caspases / Q000032:analysis; D004195:Disease Models, Animal; D004481:Ectromelia virus / Q000502:physiology*; D004482:Ectromelia, Infectious / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D053222:Fas Ligand Protein; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000473:pathology / Q000821:virology; D009000:Monocytes / Q000473:pathology / Q000821:virology; D009836:Oligodendroglia / Q000473:pathology / Q000821:virology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013997:Time Factors; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D020169:Caspases