Splenic natural killer cell activity in two models of experimental neurodegenerative diseases.
Natural killer (NK) cells are antitumour/anti-viral effectors and play important roles in shaping the immune system, but their role in neurodegenerative diseases is not clear. Here, we investigated the fate of these cells in two neurodegenerative diseases. In the first model, the activity of NK cells was examined in mice with experimental autoimmune encephalomyelitis (EAE) treated with glatiramer acetate (GA or Copaxone), a drug used to treat EAE in animals and multiple sclerosis in human. The second disease model is twitcher (Galc(twi)/Galc(twi)) mice, which represents an authentic model of human Krabbe's disease. Administration of GA ameliorated EAE in SJL mice corroborated with isolating NK cells that expressed higher killing than cells isolated from vehicle-dosed animals against immature or mature dendritic cells (DCs). However, this drug showed no effect on the numbers of NK cells or the expression of CD69 molecule. On the other hand, NK cells either disappeared from the spleens or were present in low numbers in the white pulp areas of Galc(twi)/Galc(twi) mice, which have increased D-galactosyl-beta1-1'-sphingosine (GalSph) levels. Analysis by confocal microscopy shows that NK cells found in the spleens of Galc(twi)/Galc(twi) mice were apoptotic. Incubating NK cells in vitro with GalSph induced the apoptosis in these cells, confirming the results of twitcher mice. Our results provide the first evidence showing that amelioration of EAE in mice is corroborated with NK cell lysis of antigen-presenting DCs, whereas NK cell distribution into the spleen is altered in a devastating lipid disorder corroborated with induction of their apoptosis.
Al-Falahi
Yassin
Y
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Sand
Kristin L
KL
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Knudsen
Eirunn
E
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Damaj
Bassam B
BB
Bio-Quant, Inc., San Diego, CA, USA.
Rolin
Johannes
J
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
Maghazachi
Azzam A
AA
Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D013154:Spleen / Q000276:immunology* / Q000473:pathology