Vascular endothelial growth factor/semaphorin/neuropilin interactions at sympathetic neurovascular junctions

Abstract

Several lines of evidence suggest that vascular endothelial growth factor (VEGF) and semaphorin (sema) interact via neuropilin (npn) receptors to modulate axon growth. The present study tests the hypothesis that VEGF/sema/npn interactions modulate axon growth at sympathetic neurovascular junctions. RT-PCR and western analyses indicate that VEGF, sema and npn-1 are expressed at sympathetic neurovascular junctions (SNJ). Neutralization of VEGF (VEGF Ab) decreased outgrowth of axons from explanted sympathetic ganglia. Axon growth in the presence of VEGF Ab (248 + 68 mm) was less than that in the absence of antibody (830 + 201 mm; p = 0.05; unpaired t-test; n = 4). We have previously shown that inhibition of sema binding to npn-1 promotes growth of sympathetic axons towards neonatal carotid arteries. Time lapse video microscopy was used to visualize rapid responses to sema in living sympathetic axons. Sema 3A (200 ng/ml for 30 minutes) collapsed sympathetic axons grown in the absence (5 out of 6) but not in the presence of VSM (0 out of 5). These data indicate that VEGF, sema, and npn-1 are present and functional at SNJs. These data also suggest a novel interaction between VSM and sympathetic neurons that may modulate the actions of sema at SNJs. These data support our hypothesis that interactions between VEGF, sema, and npn-1 contribute to the development and/or maintenance of vascular sympathetic innervation. HL076774.