Class A scavenger receptor promotes cerebral ischemic injury by pivoting microglia/macrophage polarization.
Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophages and plays an important role in immune responses. However, whether SR-A can influence microglia/macrophage polarization in cerebral ischemic injury is not known. To this end we monitored the phenotypic alteration of microglia/macrophages in an animal model of cerebral ischemia injury. SR-A was up-regulated in mouse brains 24h after permanent occlusion of middle cerebral artery (MCAO). SR-A-deficient mice displayed reduced infarct size and improved neurological function compared with wild-type mice littermate controls. Furthermore, a decrease in inflammatory F4/80(+)CD11b(+)CD45(high)CD11c(+) microglia/macrophages and attenuated nuclear factor-kappaB (NF-κB) activation was found in ischemic brains in the SR-A null mice. This was accompanied by alleviation of classically activated M1 macrophage markers and preservation of alternatively activated M2 macrophage markers. These data suggest that SR-A contributes to cerebral ischemic injury by pivoting the phenotype of microglia/macrophages to a skewed M1 polarization.
Atherosclerosis Research Center, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing 210029, China.
Y
Y
Xu
Lingling
L
Qian
Guijuan
G
Zong
K
K
Ma
X
X
Zhu
H
H
Zhang
N
N
Li
Q
Q
Yang
H
H
Bai
J
J
Ben
X
X
Li
Y
Y
Xu
Q
Q
Chen
D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D008264:Macrophages / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D051117:Scavenger Receptors, Class A / Q000276:immunology / Q000378:metabolism*
D051117:Scavenger Receptors, Class A