Activated human neutrophils express vascular endothelial growth factor (VEGF)

The neutrophil (PMN) influx in the acute inflammatory response is associated with a local increase in vascular permeability and oedema. Vascular endothelial growth factor (VEGF), a growth factor known to have potent vascular permeability-enhancing properties in addition to being an endothelial cell mitogen and a chemo-attractant for mononuclear cells, has previously been shown to be expressed by mononuclear cells and platelets, though PMN VEGF expression has not been reported. PMNs isolated from healthy adult volunteers (n = 16) were incubated for 4 h at 37 degrees C in the presence of tumour necrosis factor alpha (TNF-alpha) (5 ng/ml) and serum opsonized zymozan (SOZ) (500 micrograms/ml). Supernatant VEGF levels were measured using a sandwich antibody capture immuno-assay. Median (interquartile range) VEGF levels were significantly increased in PMN supernatants following stimulation with both TNF-alpha [347 pg/ml (264-385 pg/ml)] and SOZ [506 pg/ml (407-593 pg/ml)] compared with control values [78 pg/ml (78-87 pg/ml)]. Time course experiments with SOZ stimulated PMNs showed that the majority of VEGF production occurred within the first hour (1 h mean VEGF level 318 pg/ml, 4 h mean VEGF level 451 pg/ml). RT-PCR studies showed that PMNs express mRNA for the two common VEGF splice variants, VEGF121 and VEGF165. PMN VEGF production may be central to the classic acute phase response to injury and the chemo-attraction of other leukocytes to the source of injury.