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

Recently, vascular endothelial growth factor receptor 3 (VEGFR-3) has been shown to provide a specific marker for lymphatic endothelia in certain huma n tissues. In this study, we have investigated the expression of VEGFR-3 an d its ligands VEGF-C and VEGF-D in fetal and adult tissues. VEGFR-3 was con sistently detected in the endothelium of lymphatic vessels such as the thor acic duct, but fenestrated capillaries of several organs including the bone marrow, splenic and hepatic sinusoids, kidney glomeruli and endocrine glan ds 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, i ntense cytoplasmic staining for VEGF-C was observed in neuroendocrine cells such as the alpha cells of the islets of Langerhans, prolactin secreting c ells of the anterior pituitary, adrenal medullary cells, and dispersed neur oendocrine cells of the gastrointestinal tract. VEGF-D was observed in the innermost zone of the adrenal cortex and in certain dispersed neuroendocrin e cells. These results suggest that VEGF-C and VEGF-D have a paracrine func tion and perhaps a role in peptide release from secretory granules of certa in neuroendocrine cells to surrounding capillaries.