Neuroendocrine cells in the developing human lung: morphologic and functional considerations

The structure, distribution, and frequency of neuroendocrine (NE) cells in human fetal lung from early stages of development to term are described. Neuroendocrine cells were studied by electron microscopy and immunostaining for serotonin and bombesin, recently identified markers of these cells in human lung. The differentiation of NE cells within the airway epithelium proceeded centrifugally and followed the development of the bronchial tree. The first NE cells, identified at 8 weeks' gestation, appeared well-differentiated compared with adjacent epithelial cells, and were immunoreactive for serotonin. The first bombesin-immunoreactive cells were detected at 10 weeks' gestation. Fetal lungs from midgestation contained several ultrastructurally distinct NE cell types, distributed singly and in groups. Serotonin-immunoreactive cells were more frequent during early stages of development and were predominantly located in larger airways. Bombesin-immunoreactive cells became more numerous towards term and were concentrated in small peripheral airways. The well-differentiated appearance and large number of NE cells in fetal lung, and their increase in number towards term, suggest an important role for these cells during intrauterine life and neonatal adaptation. Whether this role involves neurohormonal regulation of fetal-neonatal pulmonary circulation or local (paracrine) or endocrine function requires further investigation.