Regulation of transferrin gene expression during lung development and injury.

Transferrin (TF), the major iron-transporting protein in vertebrates, is mainly synthesized in the liver. Although its source in lung is unknown, TF is a major inhibitor for lipid peroxidation and microbial propagation in lung fluid, and iron-free TF has been shown in rabbits to decrease the severity of respiratory failure and to improve surfactant activity. This study shows that TF is produced and secreted by the lung. In baboons and humans. TF gene expression displays distinct temporal patterns in different lung cells as revealed by in situ hybridization. Although expression of TF mRNA in submucosal glands remains active during development and throughout adulthood, its level in airway epithelial increases with advancing gestational age, reaches its peak before birth, declines 6-12 mo after birth, and diminishes in the older adult. In premature baboons maintained on ventilatory support, expression of TF mRNA is suppressed in both airway epithelium and glands. TF production by airway epithelia before birth most likely prevents oxidative damage in the newborn period, and its loss during injury may allow further lung damage.