Kresch M J, Christian C, Wu F, Hussain N
Department of Pediatrics, University of Connecticut School of Medicine, Farmington 06030-2948, USA.
Pediatr Res. 1998 Mar;43(3):426-31. doi: 10.1203/00006450-199803000-00020.
Apoptosis has been shown to be involved in several processes during embryogenesis, but the ontogeny of apoptosis during lung development ahs not been studied. The goals of the current study were to determine if apoptosis occurs during lung development, and to determine the ontogeny of the changes in apoptosis that occur. We studied the ontogeny of apoptosis in vivo using lungs from 14-18-d gestation fetal rats, newborn rats, and 1-d-, 2-d-, 5-d-, and 10-d-old rat pups. Apoptosis was assessed by electron microscopy and the terminal deoxyribonucleotidyl transferase dUTP nick end-labeling assay. We compared the in vivo results with explants of 14-d gestation fetal rat lung placed in culture for 1-4 d because the biochemical development of the lung in organ culture has been shown to closely parallel the development of the lung in vivo. We found apoptosis of mesenchymal cells at the periphery of distal lung buds in early fetal lung (14-16-d gestation). Apoptosis of both mesenchyme and epithelium was present in later fetal lung (18-d gestation). There were no qualitative differences in apoptosis between in vivo fetal lung and explant cultures of fetal lung. There was a 14-fold increase in apoptosis at birth and in the first postnatal day of life (9-12% of cells) compared with fetal lung (0.6-1% of cells). This was followed by a rapid decline in the percentage of apoptotic cells to fetal levels at postnatal d 2-10. We conclude that apoptosis occurs in a spatially, temporally, and cell-specific manner during lung development. The number of cells undergoing apoptosis increases dramatically in the first day after birth.
细胞凋亡已被证明参与胚胎发育的多个过程，但肺发育过程中细胞凋亡的个体发生尚未得到研究。本研究的目的是确定肺发育过程中是否发生细胞凋亡，并确定所发生的细胞凋亡变化的个体发生情况。我们使用妊娠14 - 18天的胎鼠、新生大鼠以及1日龄、2日龄、5日龄和10日龄的幼鼠的肺，对体内细胞凋亡的个体发生进行了研究。通过电子显微镜和末端脱氧核苷酸转移酶dUTP缺口末端标记法评估细胞凋亡。我们将体内实验结果与妊娠14天的胎鼠肺组织培养1 - 4天的外植体结果进行了比较，因为已证明器官培养中肺的生化发育与体内肺的发育密切平行。我们发现，在早期胎肺（妊娠14 - 16天）中，远端肺芽周边的间充质细胞发生凋亡。在后期胎肺（妊娠18天）中，间充质和上皮细胞均发生凋亡。体内胎肺与胎肺外植体培养物之间的细胞凋亡在性质上没有差异。与胎肺（0.6 - 1%的细胞）相比，出生时和出生后第一天的细胞凋亡增加了14倍（9 - 12%的细胞）。随后，凋亡细胞百分比在出生后第2 - 10天迅速下降至胎肺水平。我们得出结论，在肺发育过程中，细胞凋亡以空间、时间和细胞特异性的方式发生。出生后第一天，发生凋亡的细胞数量急剧增加。
