HYPEROXIC INJURY DECREASES ALVEOLAR EPITHELIAL-CELL EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) IN NEONATAL RABBIT LUNG

Normal neonatal lung growth requires a substantial increase in microva scular endothelial cells. Oxygen injury to neonatal lung destroys endo thelial cells and alters the normal process of alveolarization, includ ing development of the microvasculature. The mechanisms that regulate lung alveolar capillary growth and development are not known. Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelia l cells that is often expressed by epithelial cells in close proximity to capillary beds. VEGF expression is induced by hypoxia and may be i nhibited by hyperoxia. We examined the cell-specific expression of VEG F during normal postnatal lung development and the effects of hyperoxi c lung injury on VEGF mRNA and protein in vivo. Normal newborn rabbits between 1 day and 5 wk of age had VEGF transcripts located mainly in alveolar epithelial cells, with little or no VEGF mRNA noted in smooth muscle or endothelial cells. A subpopulation of freshly isolated, nor mal type II cells, but not mesenchymal cells, expressed VEGF mRNA. New born rabbits exposed to 100% oxygen for 4 days had no change in VEGF m RNA abundance, transcript location, or immunostaining. Animals exposed to 100% oxygen for an average of 9 days had an 80% decrease in lung V EGF mRNA abundance, decreased alveolar epithelial cell VEGF expression , and decreased VEGF immunostaining. Recovery of VEGF expression to co ntrol levels occurred during a 5-day recovery period. We conclude that alveolar epithelial cells in postnatal lung express VEGF, suggesting epithelial regulation of alveolar capillary formation. Furthermore, hy peroxic injury decreases neonatal lung VEGF mRNA and protein, which ma y be a contributory mechanism of impaired postnatal microvascular deve lopment in oxygen injury.