IMMUNOLOCALIZATION OF TRANSFORMING GROWTH-FACTOR-ALPHA, EPIDERMAL GROWTH-FACTOR (EGF), AND EGF-RECEPTOR IN NORMAL AND INJURED DEVELOPING HUMAN LUNG

The family of growth factors that includes epidermal growth factor (EG F) and transforming growth factor-alpha (TGF-alpha) are thought to pla y a role in the regulation of fetal lung development and epithelial re pair after injury. To further elucidate the potential role of these gr owth factors and their receptor in normal human lung development and i n response to injury, their distribution was determined by immunohisto chemistry in normal fetal lung, as well as both normal and injured pos tnatal human lung. We studied 14 specimens of human lung tissue: from three fetuses, four normal infants, two preterm infants with hyaline m embrane disease, and five infants with late bronchopulmonary dysplasia (BPD). EGF, TGF-alpha, and EGF receptor (EGF-R) colocalized in airway epithelium in normal fetal and in postnatal human lung. They were als o colocalized in scattered alveolar epithelial cells in postnatal lung . Large numbers of alveolar macrophages immunostained for EGF, TGF-alp ha, and EGF-R in lungs with late stages of BPD. The colocalization of these growth factors suggests parallel expression of EGF family member s. Moreover, the colocalization of these growth factors with their rec eptor in developing lung suggests that they may act through an autocri ne mechanism. The prominent expression of these growth factors in alve olar macrophages in BPD suggests they may be involved with the pathoge nesis of this disease.