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Ontogeny of epidermal growth factor receptor and lipocortin-1 in fetal and neonatal human lungs
M D Johnson1, M E Gray, G Carpenter
1Department of Pathology, Vanderbilt University, School of Medicine, Nashville, TN 37232-2370.
Insights
Epidermal growth factor (EGF) receptor and lipocortin-1 are present in developing human fetal airways and glands. Their distribution suggests a role in the proliferation of conducting airways and tracheal glands during lung development.
Area of Science:
- Developmental Biology
- Cell Biology
- Pulmonology
Background:
- The epidermal growth factor (EGF) receptor and its substrate, lipocortin-1, are crucial in cellular signaling and proliferation.
- Understanding their developmental expression in the human lung is key to comprehending airway and gland morphogenesis.
Purpose of the Study:
- To investigate the ontogeny and distribution of EGF receptor and lipocortin-1 in the developing human fetal and neonatal lung and trachea.
- To elucidate the potential roles of EGF receptor and lipocortin-1 in human airway and gland development.
Main Methods:
- Immunohistochemistry using polyclonal antibodies against EGF receptor and lipocortin-1.
- Analysis of human fetal and neonatal lung tissue samples ranging from 8 weeks' gestation to 16 days postnatal.
Main Results:
- EGF receptor immunoreactivity was observed in bronchiolar epithelium (15-32 weeks gestation), bronchial glands (from 19 weeks), and bronchial epithelium (from 23 weeks).
- Lipocortin-1 immunoreactivity was widespread in tracheal epithelium (from 10 weeks), bronchial epithelium (from 12 weeks), and developing bronchial and tracheal glands.
- Neither marker was detected in alveolar cells, fibrocytes, chondrocytes, or smooth muscle cells.
Conclusions:
- The developmental expression patterns of EGF receptor and lipocortin-1 suggest their involvement in the proliferation of conducting airways and glands in the human fetal lung.
- These findings provide insights into the molecular mechanisms regulating human lung morphogenesis.
Abstract:
The ontogeny and distribution of the epidermal growth factor (EGF) receptor and lipocortin-1, a major cellular substrate of the EGF receptor, were evaluated in a developmental series of fetal and neonatal human lungs (8 to 41 weeks' gestation and stillborn to 16 days' postnatal age). The peroxidase anti-peroxidase technique with two polyclonal antibodies recognizing the EGF receptor and one polyclonal antibody recognizing lipocortin-1 were used for immunohistochemical localization. Extensive or scattered bronchiolar EGF receptor immunoreactivity appeared in the entire series of frozen lung specimens from 15 to 32 weeks' gestation. Bronchial glands exhibited EGF receptor immunostaining from 19 weeks onward, and immunoreactivity in bronchial epithelium was detected from 23 weeks onward. Most tracheas showed extensive lipocortin-1 immunoreactivity in the epithelium beginning at 10 weeks' gestation. Immunostaining was also seen in cells lining the ducts of submucosal glands after 15 weeks' gestation and in nonmucous acinar cells of tracheal glands after their appearance at 18 weeks' gestation. Bronchial epithelium exhibited lipocortin-1 immunoreactivity from 12 weeks' gestation onward. Bronchial gland necks became immunostained from 16 weeks' gestation onward, followed by acinar immunostaining as they subsequently developed. Bronchiolar epithelium was immunostained as early as 12 weeks, beginning with the largest airways, and by 24 weeks extending distally to the bronchioloalveolar portals. Lipocortin-1 immunostaining of larger conducting airway epithelium was primarily confined to ciliated cells. Neither EGF receptor nor lipocortin-1 immunoreactivity was detected in alveolar type I or type II cells, fibrocytes, chondrocytes, or smooth muscle cells at any gestational age. These developmental patterns suggest that the EGF receptor and lipocortin-1 may participate in normal growth factor-induced proliferation of the conducting airways and their glands in the human fetal lung and trachea.