Neuroepithelial bodies and growth of the airway epithelium in developing hamster lung
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.
Jr, RFH; Sorokin, SP; McDowell, EM; McNelly, NA; Polak, JM; Scheuermann, DW; Johnson, DE; Becker, KL; Keith, IM; Cutz, E; Stephens, NL; Mossman, BT; Cuttitta, F; Sunday, ME
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