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J. Biol. Chem., Vol. 277, Issue 33, 29889-29896, August 16, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/33/29889    most recent M200868200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mitrasinovic, O. M. Articles by Murphy, G. M. Search for Related Content PubMed PubMed Citation Articles by Mitrasinovic, O. M. Articles by Murphy, G. M., Jr. Social Bookmarking                      What's this?

Accelerated Phagocytosis of Amyloid- by Mouse and Human Microglia Overexpressing the Macrophage Colony-stimulating Factor Receptor^*

From the Neuroscience Research Laboratories, Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305-5485

Microglia surrounding A 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 A. Flow cytometry and laser confocal microscopy showed accelerated phagocytosis of A 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 A 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 A. M-CSFR antibody blocking experiments demonstrated that increased A 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 A after immunization.

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