We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4<sup>+</sup> hemangiocytes.
- Authors
Jin, David K.; Shido, Koji; Kopp, Hans-Georg; Petit, Isabelle; Shmelkov, Sergey V.; Young, Lauren M.; Hooper, Andrea T.; Amano, Hideki; Avecilla, Scott T.; Heissig, Beate; Hattori, Koichi; Zhang, Fan; Hicklin, Daniel J.; Wu, Yan; Zhu, Zhenping; Dunn, Ashley; Salari, Hassan; Werb, Zena; Hackett, Neil R.; Crystal, Ronald G.
- Abstract
The mechanisms through which hematopoietic cytokines accelerate revascularization are unknown. Here, we show that the magnitude of cytokine-mediated release of SDF-1 from platelets and the recruitment of nonendothelial CXCR4+VEGFR1+ hematopoietic progenitors, 'hemangiocytes,' constitute the major determinant of revascularization. Soluble Kit-ligand (sKitL), thrombopoietin (TPO, encoded by Thpo) and, to a lesser extent, erythropoietin (EPO) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced the release of SDF-1 from platelets, enhancing neovascularization through mobilization of CXCR4+VEGFR1+ hemangiocytes. Although revascularization of ischemic hindlimbs was partially diminished in mice deficient in both GM-CSF and G-CSF (Csf2−/−Csf3−/−), profound impairment in neovascularization was detected in sKitL-deficient Mmp9−/− as well as thrombocytopenic Thpo−/− and TPO receptor–deficient (Mpl−/−) mice. SDF-1–mediated mobilization and incorporation of hemangiocytes into ischemic limbs were impaired in Thpo−/−, Mpl−/− and Mmp9−/− mice. Transplantation of CXCR4+VEGFR1+ hemangiocytes into Mmp9−/− mice restored revascularization, whereas inhibition of CXCR4 abrogated cytokine- and VEGF-A–mediated mobilization of CXCR4+VEGFR1+ cells and suppressed angiogenesis. In conclusion, hematopoietic cytokines, through graded deployment of SDF-1 from platelets, support mobilization and recruitment of CXCR4+VEGFR1+ hemangiocytes, whereas VEGFR1 is essential for their angiogenic competency for augmenting revascularization. Delivery of SDF-1 may be effective in restoring angiogenesis in individuals with vasculopathies.
- Publication
Nature Medicine, 2006, Vol 12, Issue 5, p557
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm1400