Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Aβ by microglia.
Complement component C3 and complement receptor type 3 contribute to the phagocytosis and clearance of fibrillar Aβ by microglia.
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DOI：
10.1002/glia.22331
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发表时间：
2012-05
期刊：
影响因子：
6.2
通讯作者：
Lemere, Cynthia A.
中科院分区：
文献类型：
--
作者：
Fu, Hongjun;Liu, Bin;Frost, Jeffrey L.;Hong, Soyon;Jin, Ming;Ostaszewski, Beth;Shankar, Ganesh M.;Costantino, Isabel M.;Carroll, Michael C.;Mayadas, Tanya N.;Lemere, Cynthia A.
Complement components and their receptors are found within and around Aβ 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-β (fAβ) by murine microglia in vitro and in vivo. Microglia took up not only synthetic fAβ42 but also amyloid cores from AD patients, transporting them to lysosomes in vitro. Fibrillar Aβ42 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 attenutated fibrillar Aβ42 uptake by N9 microglia. Fluorescent fibrillar Aβ42 microinjected cortically was significantly higher in C3 and Mac-1 knockout mice compared to 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 fAβ by microglia, providing support for a potential beneficial role for microglia and the complement system in AD pathogenesis.
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