Neurovascular effects of CD47 signaling: promotion of cell death, inflammation, and suppression of angiogenesis in brain endothelial cells in vitro.
The concept of the neurovascular unit emphasizes that common signals and substrates underlie the physiology and pathophysiology of neuronal and endothelial compartments in brain. Recent data suggest that activation of the integrin-associated protein CD47 promotes neuronal cell death. Is it possible that CD47 may also negatively affect cerebral endothelial cells? Exposure of wild-type primary mouse cerebral endothelial cells to the CD47 ligand thrombospondin 1 (TSP-1) induced an increasing amount of cell death, whereas cytotoxicity was significantly decreased in cerebral endothelial cells derived from CD47 knockout mice. The specific CD47-activating peptide, 4N1K, similarly induced cell death in human brain microvascular endothelial cells. Promotion of inflammation was also involved because lower TSP-1 was able to up-regulate the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Finally, CD47 signaling may suppress angiogenesis because 4N1K significantly inhibited endothelial cell migration and tube formation in vitro. We conclude that CD47 signaling can negatively affect the viability and function of cerebral endothelial cells, further supporting the notion that CD47 may be a potential neurovascular target for stroke and brain injury.
Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
Changhong
C
Xing
Sunryung
S
Lee
Woo Jean
WJ
Kim
Hui
H
Wang
Yong-Guang
YG
Yang
MingMing
M
Ning
Xiaoying
X
Wang
Eng H
EH
Lo
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000276:immunology / Q000502:physiology*; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology; D015213:Neuroimmunomodulation / Q000502:physiology; D009842:Oligopeptides / Q000378:metabolism; D019700:Thrombospondin 1 / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C120273:4N1K peptide; D051928:CD47 Antigen; C497894:CD47 protein, human; C497895:Cd47 protein, mouse; D009842:Oligopeptides; D019700:Thrombospondin 1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1