Ji C M, Plopper C G, Pinkerton K E
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, USA.
Am J Respir Cell Mol Biol. 1995 Aug;13(2):144-51. doi: 10.1165/ajrcmb.13.2.7626284.
Postnatal differentiation of nonciliated bronchiolar epithelial (Clara) cells occurs in a wave-like pattern beginning in the upper airways and ending in the terminal bronchiole. The heterogeneity of Clara cell differentiation observed during postnatal development in rats may be due to both cell turnover rate and cell position in the airways. To test the importance of these two factors in Clara cell differentiation, terminal bronchioles were examined in rats from gestational day 21 through postnatal day 100. The volume fraction of smooth endoplasmic reticulum (SER), a marker of differentiation, was seen to increase with age, while the epithelial cell labeling index of terminal bronchioles decreased over the same period. This represented a significant inverse correlation between SER volume density and cell proliferation rates (r2 = 0.80, P < 0.02). To evaluate the importance of cell position as a factor in cellular differentiation, the abundance of SER and secretory granules and the expression of cytochrome P450 isozyme 2B in Clara cells were examined along the entire length of the terminal bronchiole in animals 1, 21, and 100 days of age. For all three characteristics, Clara cells showed a similar degree of maturation from the proximal bronchiolar bifurcation to the bronchiole-alveolar duct junction (BADJ) (a span of approximately 35 cells). We conclude that during prenatal and postnatal bronchiolar development in rats: (1) the Clara cell is the most actively dividing cell type for the lower airways; (2) the stage of Clara cell differentiation is inversely related to Clara cell mitotic activity; and (3) the heterogeneity of Clara cell maturation and mitotic activity is not influenced by position within the terminal bronchiole.
无纤毛细支气管上皮（克拉拉）细胞的出生后分化呈波浪状模式，始于上呼吸道，止于终末细支气管。在大鼠出生后发育过程中观察到的克拉拉细胞分化的异质性可能是由于细胞更新率和气道中的细胞位置。为了测试这两个因素在克拉拉细胞分化中的重要性，对妊娠第21天至出生后第100天的大鼠终末细支气管进行了检查。作为分化标志物的滑面内质网（SER）的体积分数随年龄增加，而同期终末细支气管的上皮细胞标记指数下降。这代表了SER体积密度与细胞增殖率之间存在显著的负相关（r2 = 0.80，P < 0.02）。为了评估细胞位置作为细胞分化因素的重要性，在1日龄、21日龄和100日龄动物的终末细支气管全长中检查了克拉拉细胞中SER和分泌颗粒的丰度以及细胞色素P450同工酶2B的表达。对于所有这三个特征，克拉拉细胞从近端细支气管分叉到细支气管 - 肺泡管连接处（BADJ）（约35个细胞的跨度）显示出相似程度的成熟。我们得出结论，在大鼠产前和产后细支气管发育过程中：（1）克拉拉细胞是下呼吸道中最活跃分裂的细胞类型；（2）克拉拉细胞分化阶段与克拉拉细胞有丝分裂活性呈负相关；（3）克拉拉细胞成熟和有丝分裂活性的异质性不受终末细支气管内位置的影响。
