VEGF-C and VEGF-D expression in neuroendocrine cells and their receptor, VEGFR-3, in fenestrated blood vessels in human tissues

FASEB J. 2000 Oct;14(13):2087-96. doi: 10.1096/fj.99-1049com.


Recently, vascular endothelial growth factor receptor 3 (VEGFR-3) has been shown to provide a specific marker for lymphatic endothelia in certain human tissues. In this study, we have investigated the expression of VEGFR-3 and its ligands VEGF-C and VEGF-D in fetal and adult tissues. VEGFR-3 was consistently detected in the endothelium of lymphatic vessels such as the thoracic duct, but fenestrated capillaries of several organs including the bone marrow, splenic and hepatic sinusoids, kidney glomeruli and endocrine glands also expressed this receptor. VEGF-C and VEGF-D, which bind both VEGFR-2 and VEGFR-3 were expressed in vascular smooth muscle cells. In addition, intense cytoplasmic staining for VEGF-C was observed in neuroendocrine cells such as the alpha cells of the islets of Langerhans, prolactin secreting cells of the anterior pituitary, adrenal medullary cells, and dispersed neuroendocrine cells of the gastrointestinal tract. VEGF-D was observed in the innermost zone of the adrenal cortex and in certain dispersed neuroendocrine cells. These results suggest that VEGF-C and VEGF-D have a paracrine function and perhaps a role in peptide release from secretory granules of certain neuroendocrine cells to surrounding capillaries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Antibody Specificity
  • Blood Vessels / anatomy & histology
  • Blood Vessels / chemistry*
  • Endocrine Glands / metabolism
  • Endothelial Growth Factors / genetics
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / isolation & purification*
  • Endothelium, Vascular / anatomy & histology
  • Endothelium, Vascular / chemistry*
  • Female
  • Fetus
  • Humans
  • Immunohistochemistry
  • Lymphatic System / chemistry
  • Neurosecretory Systems / chemistry*
  • Pregnancy
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / isolation & purification*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / isolation & purification*
  • Tissue Distribution
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Vascular Endothelial Growth Factor Receptor-3


  • Endothelial Growth Factors
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor D
  • Receptor Protein-Tyrosine Kinases
  • Vascular Endothelial Growth Factor Receptor-3