Microglial overexpression of the M-CSF receptor augments phagocytosis of opsonized Abeta.
The role of microglia in Alzheimer's disease (AD) has come under intense scrutiny recently because microglia may clear amyloid beta (Abeta) by phagocytosis after immunization of transgenic mice. Increased expression of the macrophage colony-stimulating factor receptor (M-CSFR) is an important feature of microglia in AD and transgenic mouse models for AD. Increased expression of M-CSFR on mouse and human microglia accelerates phagocytosis of aggregated Abeta in part through macrophage scavenger receptors. We now show that Abeta phagocytosis by microglia overexpressing M-CSFR is further enhanced by antibody opsonization of Abeta. M-CSFR overexpression increased microglial phagocytosis of opsonized aggregated Abeta in culture medium, and accelerated ingestion of native Abeta from AD brain sections. M-CSFR overexpression also increased microglial expression of Fcgamma receptors, and blocking Fcgamma receptors attenuated the enhanced Abeta uptake observed after M-CSFR overexpression and antibody opsonization. Microglia in AD and in AD mouse models with increased expression of M-CSFR are likely to rapidly ingest opsonized Abeta after immunization, making high intracerebral antibody titers unnecessary.
Mitrasinovic
Olivera M
OM
Department of Psychiatry & Behavioral Sciences, Neuroscience Research Laboratories, Stanford University School of Medicine, Stanford, CA 94305, USA.
Murphy
Greer M
GM
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D009895:Opsonin Proteins / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology
D016229:Amyloid beta-Peptides; D015703:Antigens, CD; D009895:Opsonin Proteins; D017452:Receptors, IgG; D016186:Receptor, Macrophage Colony-Stimulating Factor