| First Author | Fu H | Year | 2012 |
| Journal | Glia | Volume | 60 |
| Issue | 6 | Pages | 993-1003 |
| PubMed ID | 22438044 | Mgi Jnum | J:183868 |
| Mgi Id | MGI:5319446 | Doi | 10.1002/glia.22331 |
| Citation | Fu H, et al. (2012) Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Abeta by microglia. Glia 60(6):993-1003 |
| abstractText | Complement components and their receptors are found within and around amyloid beta (Abeta) cerebral plaques in Alzheimer's disease (AD). Microglia defend against pathogens through phagocytosis via complement component C3 and/or engagement of C3 cleavage product iC3b with complement receptor type 3 (CR3, Mac-1). Here, we provide direct evidence that C3 and Mac-1 mediate, in part, phagocytosis and clearance of fibrillar amyloid-beta (fAbeta) by murine microglia in vitro and in vivo. Microglia took up not only synthetic fAbeta(42) but also amyloid cores from patients with AD, transporting them to lysosomes in vitro. Fibrillar Abeta(42) uptake was significantly attenuated by the deficiency or knockdown of C3 or Mac-1 and scavenger receptor class A ligands. In addition, C3 or Mac-1 knockdown combined with a scavenger receptor ligand, fucoidan, further attenuated fibrillar Abeta(42) uptake by N9 microglia. Fluorescent fibrillar Abeta(42) microinjected cortically was significantly higher in C3 and Mac-1 knockout mice compared with wild-type mice 5 days after surgery, indicating reduced clearance in vivo. Together, these results demonstrate that C3 and Mac-1 are involved in phagocytosis and clearance of fAbeta by microglia, providing support for a potential beneficial role for microglia and the complement system in AD pathogenesis. (c) 2012 Wiley Periodicals, Inc. |
