Neuropilin-1 on hematopoietic cells as a source of vascular development

Yoshihiro Yamada, Yuichi Oike, Hisao Ogawa, Yasuhiro Ito, Hajime Fujisawa, Toshio Suda, Nobuyuki Takakura

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Abstract

Neuropilin-1 (NP-1) is a receptor for vascular endothelial growth factor-165 (VEGF165) and acts as a coreceptor that enhances the function of VEGF165 through VEGF receptor-2 (VEGFR-2). Studies using transgenic and knock-out mice of NP-1 indicated that this molecule is important for vascular development as well as neuronal development. We recently reported that clustered soluble NP-1 phosphorylates VEGFR-2 on endothelial cells with a low dose of VEGF165 and rescues the defective vascularity of the NP-1-/- embryo in vitro and in vivo. Here we show that NP-1 is expressed by CD45+ hematopoietic cells in the fetal liver, can bind VEGF165, and phosphorylates VEGFR-2 on endothelial cells. CD45+NP-1+ cells rescued the defective vasculogenesis and angiogenesis in the NP-1-/- P-Sp (para-aortic splanchnopleural mesodermal region) culture, although CD45+NP-1+ cells did not. Moreover, CD45+NP-1+ cells together with VEGF165 induced angiogenesis in an in vivo Matrigel assay and cornea neovascularization assay. The extracellular domain of NP-1 consists of "a," "b," and "c" domains, and it is known that the "a" and "c" domains are necessary for dimerization of NP-1. We found that both the "a" and "c" domains are essential for such rescue of defective vascularities in the NP-1 mutant. These results suggest that NP-1 enhances vasculogenesis and angiogenesis exogenously and that dimerization of NP-1 is important for enhancing vascular development. In NP-1-/- embryos, vascular sprouting is impaired at the central nervous system (CNS) and pericardium where VEGF is not abundant, indicating that NP-1-expressing cells are required for normal vascular development.

Original languageEnglish
Pages (from-to)1801-1809
Number of pages9
JournalBlood
Volume101
Issue number5
DOIs
Publication statusPublished - 2003 Mar 1

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Yamada, Y., Oike, Y., Ogawa, H., Ito, Y., Fujisawa, H., Suda, T., & Takakura, N. (2003). Neuropilin-1 on hematopoietic cells as a source of vascular development. Blood, 101(5), 1801-1809. https://doi.org/10.1182/blood-2002-01-0119