Microglial activation by uptake of fDNA via a scavenger receptor.
The fate of the fragmented DNA (fDNA) observed in neuronal nuclei in Alzheimer brain is unknown. However, its fate is suggested as fDNA is found in the cytoplasm of adjacent activated microglia. After a brief incubation with fDNA, approximately 70% of microglia had fDNA in their cytoplasm, were activated, and overexpressed interleukin-1beta. Microglial activation enhanced uptake whereas blocking scavenger receptors suppressed this uptake. These results suggest that the brain rids itself of fDNA from dying neurons through microglial uptake, activation, and overexpression of IL-1. Such overexpression of IL-1 in Alzheimer brain has been linked to Alzheimer pathogenesis.
Li
Yuekui
Y
Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Liu
Ling
L
Liu
Dongge
D
Woodward
S
S
Barger
Steven W
SW
Mrak
Robert E
RE
Griffin
W Sue T
WS
D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001692:Biological Transport; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000503:physiopathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004247:DNA / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling / Q000379:methods; D007371:Interferon-gamma / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051122:Scavenger Receptors, Class B
D000906:Antibodies; D000970:Antineoplastic Agents; D008565:Membrane Proteins; D011134:Polysaccharides; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D007371:Interferon-gamma; D004247:DNA; C007789:fucoidan