Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets

Low oxygen (O-2) is the key stimulus for expression of vascular endothelial growth factor (VEGF) in several adherent cells. Whether hypoxia also direc ts the release of VEGF protein from neutrophils (polymorphonuclear neutroph ils; PMN) and platelets has not been investigated. We therefore compared VE GF release of platelets, PMN, and human vascular smooth muscle cells (HSMC) in response to hypoxia with that to activators of cellular degranulation. In contrast to HSMC, VEGF release from PMN and platelets or VEGF mRNA expre ssion in PMN was not stimulated under hypoxic conditions (1% O-2). Hypo- or hyperthermia and acidosis, other conditions potentially associated with is chemic and inflammatory tissue injury, also did not stimulate VEGF secretio n from PMN. However, stimulation of platelets with thrombin and of PMN with phorbol 12-myristate 13-acetate induced a time-dependent release of VEGF, peaking after 30 and 60 min, respectively. This was blocked by the degranul ation inhibitor pentoxifylline but not by the protein-synthesis inhibitor c ycloheximide. We conclude that rapid release of VEGF from platelets and PMN may occur independently of oxygenation during inflammation and hemostasis.