Myeloid progenitor cell regulatory effects of vascular endothelial cell growth factor

Hal E. Broxmeyer, Scott Cooper, Zhi Hua Li, Li Lu, Ho Yeong Song, Byoung Se Kwon, Robert E. Warren, David B. Donner

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Vascular endothelial cell growth factor (VEGF) is a ligand for the tyrosine kinase receptor Flk-1/KDR and Flt1 and is considered to be an endothelial cell specific mitogen that plays an important role in angiogenesis. Since Flk-1 mRNA has been detected in primitive and more mature hematopoietic cells, recombinant human VEGF was evaluated for its influence on hematopoiesis, which was assayed as in vitro colony formation by myeloid progenitor cells from human bone marrow. VEGF enhanced colony formation by mature subsets of granulocyte-macrophage and erythroid progenitor cells that had been stimulated with a colony stimulating factor. In contrast, VEGF inhibited colony formation by more immature subsets of granulocyte-macrophage, erythroid and multipotential progenitor cells synergistically stimulated to proliferate with a colony stimulating factor and either steel factor or the ligand for the Flt-3 receptor tyrosine kinase. VEGF produced effects similar to those given above on purified CD34+++ progenitor cells from bone marrow and VEGF effects were neutralized by VEGF antibodies. However, when assessed for effects on single sorted CD34+++ cells, VEGF only enhanced or suppressed colony formation by granulocyte-macrophage progenitor cells and the amplitude of the response was less than that observed when populations of these cells were tested. In the single cell assays, VEGF had no effect on colony formation by erythroid or multipotential progenitors. These results suggest that the effects of VEGF, which were not species specific, are mediated by both direct and indirect actions on the progenitors and thereby identify new activities for this important factor.

Original languageEnglish (US)
Pages (from-to)203-215
Number of pages13
JournalInternational Journal of Hematology
Volume62
Issue number4
DOIs
StatePublished - Dec 1995

Keywords

  • CD34-accessory cells
  • Myeloid progenitor cells
  • Vascular endothelial cell growth factor

ASJC Scopus subject areas

  • Hematology

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