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.