Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils

作者：Ohki Y; Heissig B; Sato Y; Akiyama H; Zhu ZP; Hicklin DJ; Shimada K; Ogawa H; Daida H; Hattori K^*; Ohsaka A

来源：The FASEB Journal, 2005, 19(12): 2005-+.

DOI：10.1096/fj.04-3496fje

• angiogenesis
• hematopoietic cells
• angiogenic factors
• VEGF receptors

The granulocyte colony-stimulating factor (G-CSF) promotes angiogenesis. However, the exact mechanism is not known. We demonstrate that vascular endothelial growth factor ( VEGF) was released by Gr-1(+) CD11b(-) neutrophils but not Gr-1(-)CD11b(+) monocytes prestimulated with GCSF in vitro and in vivo. Similarly, in vivo, concomitant with an increase in neutrophil numbers in circulation, G-CSF augmented plasma VEGF level in vivo. Local G-CSF administration into ischemic tissue increased capillary density and provided a functional vasculature and contributed to neovascularization of ischemic tissue. Blockade of the VEGF pathway abrogated G-CSF-induced angiogenesis. On the other hand, as we had shown previously, VEGF can induce endothelial progenitor cell ( EPC) mobilization. Here, we show that G-CSF also augmented the number of circulating VEGF receptor-2 (VEGFR2) EPCs as compared with untreated controls. Blocking the VEGF/VEGFR1, but to a much lesser extent, the VEGF/VEGFR2 pathway in GCSF-treated animals delayed tissue revascularization in a hindlimb model. These data clearly show that G-CSF modulates angiogenesis by increasing myelomonocytic cells (VEGFR1(+) neutrophils) and their release of VEGF. Our results indicated that administration of G-CSF into ischemic tissue provides a novel and safe therapeutic strategy to improve neovascularization.

• 出版日期2005-10
• 单位河北医科大学