ACTIVATED HUMAN NEUTROPHILS EXPRESS VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF)

The neutrophil (PMN) influx in the acute inflammatory response is asso ciated with a local increase in vascular permeability and oedema, Vasc ular endothelial growth factor (VEGF), a growth factor known to have p otent vascular permeability-enhancing properties in addition to being an endothelial cell mitogen and a chemo-attractant for mononuclear cel ls, has previously been shown to be expressed by mononuclear cells and platelets, though PMN VEGF expression has not been reported. PMNs iso lated from healthy adult volunteers (n = 16) were incubated for 4 h at 37 degrees C in the presence of tumour necrosis factor alpha (TNF-alp ha) (5 ng/ml) and serum opsonized zymozan (SOZ) (500 mu g/ml). Superna tant VEGF levels were measured using a sandwich antibody capture immun e-assay. Median (interquartile range) VEGF levels were significantly i ncreased 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)] compa red with control values [78 pg/ml (78-87 pg/ml)]. Time course experime nts with SOZ stimulated PMNs showed that the majority of VEGF producti on occurred within the first hour (Ih mean VEGF level 318 pg/ml, 4 h m ean VEGF level 451 pg/ml), RT-PCR studies showed that PMNs express mRN A for the two common VEGF splice variants, VEGF(121) and VEGF(165). PM N VEGF production may be central to the classic acute phase response t o injury and the chemo-attraction of other leukocytes to the source of injury. (C) 1998 Academic Press Limited.