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Accelerated Phagocytosis of Amyloid-β by Mouse and Human Microglia Overexpressing the Macrophage Colony-stimulating Factor Receptor
Microglia surrounding Aβ plaques in Alzheimer's disease and in the APPV717F transgenic mouse model of Alzheimer's disease have enhanced immunoreactivity for the macrophage colony-stimulating factor receptor (M-CSFR), encoded by the proto-oncogene c -fms . Increased expression of M-CSFR on...
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Published in: | The Journal of biological chemistry 2002-08, Vol.277 (33), p.29889 |
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Main Authors: | , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Microglia surrounding Aβ plaques in Alzheimer's disease and in the APPV717F transgenic mouse model of Alzheimer's disease
have enhanced immunoreactivity for the macrophage colony-stimulating factor receptor (M-CSFR), encoded by the proto-oncogene
c -fms . Increased expression of M-CSFR on cultured microglia results in proliferation and release of pro-inflammatory cytokines
and expression of inducible nitric-oxide synthase. We transfected mouse BV-2 and human SV-A3 microglia to overexpress M-CSFR
and examined microglial phagocytosis of fluorescein-conjugated Aβ. Flow cytometry and laser confocal microscopy showed accelerated
phagocytosis of Aβ in mouse and human microglia because of M-CSFR overexpression that was time- and concentration-dependent.
In contrast, microglial uptake of 1-μm diameter polystyrene microspheres was not enhanced by M-CSFR overexpression. Microglial
uptake of Aβ was blocked by cytochalasin D, which inhibits phagocytosis. M-CSFR overexpression increased the mRNA for macrophage
scavenger receptor A, and fucoidan blocking of macrophage scavenger receptors inhibited uptake of Aβ. M-CSFR antibody blocking
experiments demonstrated that increased Aβ uptake depended on the interaction of the M-CSFR with its ligand. These results
suggest that overexpression of M-CSFR in APPV717F mice may prime microglia for phagocytosis of Aβ after immunization. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.M200868200 |