Loading…

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...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2002-08, Vol.277 (33), p.29889
Main Authors: Olivera M. Mitrasinovic, Greer M. Murphy, Jr
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M200868200