ApoE attenuates unresolvable inflammation by complex formation with activated C1q
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
复制标题
ApoE 通过与活化的 C1q 形成复合物来减轻无法解决的炎症
DOI：
10.1038/s41591-018-0336-8
复制
发表时间：
2019-03-01
期刊：
影响因子：
82.9
通讯作者：
Habenicht, Andreas J. R.
中科院分区：
文献类型：
--
作者：
Yin, Changjun;Ackermann, Susanne;Habenicht, Andreas J. R.
Apolipoprotein-E (ApoE) has been implicated in Alzheimer's disease, atherosclerosis, and other unresolvable inflammatory conditions but a common mechanism of action remains elusive. We found in ApoE-deficient mice that oxidized lipids activated the classical complement cascade (CCC), resulting in leukocyte infiltration of the choroid plexus (ChP). All human ApoE iso-forms attenuated CCC activity via high-affinity binding to the activated CCC-initiating C1q protein (K-D similar to 140-580 pM) in vitro, and C1q-ApoE complexes emerged as markers for ongoing complement activity of diseased ChPs, A beta plaques, and atherosclerosis in vivo. C1q-ApoE complexes in human ChPs, A beta plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Treatment with small interfering RNA (siRNA) against C5, which is formed by all complement pathways, attenuated murine ChP inflammation, A beta-associated microglia accumulation, and atherosclerosis. Thus, ApoE is a direct checkpoint inhibitor of unresolvable inflammation, and reducing C5 attenuates disease burden.
