Analysis of the Impact of CD200 on Phagocytosis.
One factor that impacts on microglial activation is the interaction between the ubiquitously expressed CD200 and CD200R, which is expressed only on microglia in the brain. Decreased signalling through CD200R, when CD200 expression is reduced, results in microglial activation and may, at least in part, explain the increased cell activity that is observed with age, in models of Alzheimer's and Parkinson's disease as well as in the human diseases. There is evidence of increased microglial activation in CD200-deficient mice, and isolated microglia prepared from these mice are more reactive to inflammatory stimuli like Toll-like receptor 2 and 4 agonists, and interferon-γ. Here, we examined the impact of CD200 deficiency on amyloid-β (Aβ)-induced changes in microglia and report, perhaps unexpectedly, that the effect of Aβ was attenuated in microglia prepared from CD200-deficient mice. The evidence indicates that this is a consequence of increased phagocytosis, associated with increased lysosomal activity in CD200-deficient microglia. The data suggest that mTOR-related signalling is decreased in these cells and that inhibiting mTOR by rapamycin increases phagocytosis. Thus, while the findings to date have emphasized the anti-inflammatory effects of CD200-CD200R interaction, the present evidence indicates a previously unreported impact on lysosomal function.
['Lyons|Anthony|A|', 'Minogue|Aedín M|AM|', 'Jones|Raasay S|RS|', 'Fitzpatrick|Orla|O|', 'Noonan|Janis|J|', 'Campbell|Veronica A|VA|', 'Lynch|Marina A|MA|']
D016229:Amyloid beta-Peptides D000818:Animals D015703:Antigens, CD D006624:Hippocampus D007371:Interferon-gamma D008247:Lysosomes D008262:Macrophage Activation D008297:Male D017628:Microglia D010587:Phagocytosis D017208:Rats, Wistar D051195:Toll-Like Receptor 2
CD200 Phagocytosis Microglial activation Amyloid-β Lysosome