Localization of epidermal growth factor receptor in alveolar epithelium during human fetal lung development in vitro.
Epidermal growth factor (EGF) enhances alveolar type II cell differentiation. In human fetal lung explants, EGF stimulates surfactant protein A (SP-A) synthesis. This effect may occur through a direct interaction of the ligand on EGF receptors located within distal pulmonary epithelium during alveolar type II cell differentiation. To determine if EGF receptor is present in alveolar epithelium, immunostaining for EGF receptor and in situ hybridization for EGF receptor mRNA were performed in human fetal lung explants undergoing alveolar type II cell differentiation in vitro. After 4 days in culture, EGF receptor immunostaining was present in alveolar epithelium from human fetal lung explants compared to minimal immunostaining in undifferentiated human fetal lung epithelium prior to culture. In situ hybridization revealed increased EGF receptor mRNA in differentiated type II cells from cultured explants, with minimal EGF receptor mRNA detected in undifferentiated epithelium from tissue prior to culture. Immunogold staining revealed EGF receptors on the cytoplasmic membranes of epithelial cells lining the prealveolar ducts in human fetal lung explants after 2 days in culture. Alveolar type II cell differentiation in vitro was confirmed ultrastructurally by the presence of lamellar bodies and biochemically by an increase in SP-A content. Thus, EGF receptor is found in alveolar epithelium during differentiation, which suggests an important role for EGF during human fetal lung development.
Klein
J M
JM
Department of Pediatrics, University of Iowa, Iowa City 52242-1083, USA.
Fritz
B L
BL
McCarthy
T A
TA
Wohlford-Lenane
C L
CL
Snyder
J M
JM
D005314:Embryonic and Fetal Development; D004848:Epithelium / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005333:Fetus / Q000737:chemistry*; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008168:Lung / Q000196:embryology; D008854:Microscopy, Electron; D011510:Proteolipids / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000737:chemistry* / Q000166:cytology / Q000196:embryology; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D066246:ErbB Receptors