VEGFR-1 signaling regulates the homing of bone marrow-derived cells in a mouse stroke model.
Vascular endothelial growth factor receptor 1 (VEGFR-1) is highly expressed in endothelial cells and regulates developmental angiogenesis by acting as a decoy receptor and trapping VEGF-A. Vascular endothelial growth factor receptor 1 is also expressed in monocytes and macrophages; mice lacking the VEGFR-1 tyrosine kinase (TK) domain (VEGFR-1 TK mice) display impaired macrophage function. Because macrophages are recruited to sites of cerebral ischemic infarcts, we hypothesized that lack of VEGFR-1 TK in bone marrow(BM) cells would affect the outcome in an experimental stroke model. We performed BM transplantation experiments in C57BL/6J mice using VEGFR-1 TK and VEGFR-1 TK mice as BM donors and analyzed cell infiltration after cerebral ischemia. There was reduced initial recruitment of VEGFR-1 TK myeloid cells into the infarcted tissue and reduced postischemic angiogenesis at 3days postischemia. By 10 days, the numbers of infiltrating cells and the densities of vessels in the infarct peri-infarct zone were similar for both groups. Neither infarct size at 3 and 10 days postischemia nor neurological performance at 24 hours was different between the experimental groups. These results support a role of VEGFR-1 signaling in the early regulation of BM infiltration and angiogenesis after brain ischemia.
Beck
Heike
H
Walter Brendel Center of Experimental Medicine, Institute of Cardiovascular Physiology, Ludwig-Maximilians University Munich, Munich, Germany. Heike.Beck@med.uni-muenchen.de
Raab
Sabine
S
Copanaki
Ekaterini
E
Heil
Matthias
M
Scholz
Alexander
A
Shibuya
Masabumi
M
Deller
Thomas
T
Machein
Marcia
M
Plate
Karl H
KH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002545:Brain Ischemia / Q000150:complications; D002454:Cell Differentiation; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D007150:Immunohistochemistry; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia; D015398:Signal Transduction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000172:deficiency / Q000378:metabolism*
D040281:Vascular Endothelial Growth Factor Receptor-1