Neuroepithelial bodies and growth of the airway epithelium in developing hamster lung

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Abstract
Clusters of small-granule endocrine cells, neuroepithelial bodies (NEBs), appear in the airway lining of pseudoglandular lungs, but their prenatal function has remained obscure. Transplacental labeling of S-phase cells in Syrian golden hamsters has allowed us to relate NEBs to patterns of replication in the surrounding endoderm. Two methods were used: (1) continuous exposure to 3H-thymidine for the last 25% (4 days) of gestation, and 2) 2-hr exposure to 5-bromo-2′-deoxyuridine (BrdU) on fetal day 15. 3H-thymidine incorporation was assessed in autoradiographs of neonatal lung by grain counting from 923 nonendocrine and 251 endocrine cells in 28 airway epithelial terrains, each centered on a NEB: 12 in the perihilar, 8 in the middle, and 8 in the distal third of the left axial bronchus. Grain densities for 10–25 nonendocrine cells on either side of the NEB were plotted vs. position relative to the endocrine cell cluster and analyzed by rank-order correlation and linear regression. Label was highest in cells closest to NEBs in all 12 terrains (P < 0.05–0.001) in the perihilar airway, in 3 of 8 terrains (P < 0.025–0.001) in the middle third of the bronchus, and in respective, pooled populations (P < 0.001). The effect was not demonstrable in the distal third of the airway. In the 15-day fetus 243 mm of airway perimeter were measured and 3,218 BrdU-labeled epithelial cells counted from sections through the entire length of the left axial airway and the lobar bronchus, intermediate, and terminal bronchioles of the infracardiac (IC) lobe. Overall, 43% of BrdU-labeled cells and only 24% of epithelium lay within 20 μm of NEBs. Preferential concentration of S-phase cells around NEBs was significant (P < 0.001) by X2 test at all airway levels. Net density of NEB-associated BrdU + cells was 10/mm of basal lamina in the trachea, rose distally along the left axial airway to 22/mm at the end of the undivided bronchus, and fell to 15/mm in the terminal channels. It was 9 cells/mm in terminal bronchioles of the infracardiac lobe. Regional differences in 3H-thymidine and BrdU labeling patterns can be correlated with differences in the age of NEBs. We conclude that NEBs regulate local cell proliferation in developing hamster airway, probably activated in a proximal-to-distal wave reflecting maturational changes in the NEBs along the same gradient.