Cell Kinetics of Normal Adult Hamster Bronchial Epithelium in the Steady State

Abstract

To establish the progenitor role of bronchial epithelial cells in the steady state, we undertook a quantitative autoradiographic study in normal hamsters. Groups of 7 hamsters were killed 1 h and 1, 2, 3, 4, 7, and 14 d after an intraperitoneal injection of [3H]thymidine (2 microCi/g body wt). Autoradiograms were prepared from 861 Epon sections, 2 microns thick, of left intrapulmonary hilar bronchi. Epithelial cells were classified into 1 of 7 categories: basal-1 (B1) and basal-2 (B2), depending on nuclear height; secretory cells denoted as S1 with zero to 4 granules, S2 with 5 or more granules with intervening cytoplasm, and S3 with abundant granules completely filling the cytoplasm; ciliated (C); and indeterminate (IN). Mean silver grain counts decreased significantly over time only for B1 cells (P less than 0.05), with a cell cycle time of 20.6 d and a DNA synthetic time of 7.5 h. Labeled cells, 1 h after thymidine injection, comprised 30.5% S1, 27.8% B1, 22.8% B2, 6.8% IN, 6.4% S2, 5.7% C, and 0% S3 cells. Labeling indices of individual cell categories (LIc), at 1 h after labeling, were highest for B1 followed by B2 cells, reflecting their proliferative intensity. Labeling index of all epithelial cells combined did not change with time, indicating that there was no major cell death or label dilution. The LIc decreased significantly over time only for B1 and B2 cells (P less than 0.001 and P less than 0.002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular Mechanisms of Metaplasia, Differentiation and Hyperplasia of Goblet Cellin Allergic Asthma

“…There is differential expression of these proteins in airway BCs. At steady state, most mouse tracheal BCs express KRT5, whereas only a subset expresses KRT14 [82]. Mouse BCs generated lineage-labeled basal, ciliated and Clara cells [15].…”

“…By contrast, lineagelabeledClara cells expressing SCGB1A1 + cellsin the trachea proliferate and generate ciliated cells but a population was replaced over time by unlabeled progenitor cells, presumably BCs [12]. This suggests that, in airway epithelia containing BCs, the Clara cells do not function as stem cells over the long term under normal conditions.On the other hand, Randell [80] reviewed that both BCs and nonciliated columnar epithelial cells of the rodent trachea proliferate in the steady state and in response to injury [81,82]. BCs can regenerate a fully differentiated mucociliary epithelium when seeded in denuded tracheas (host tracheas that have been stripped of their epithelium) and transplanted subcutaneously in nude rats [83,84].…”

Airway Epithelial Stem Cells and the Pathophysiology of Chronic Obstructive Pulmonary Disease

“…In the 1960s, Blenkinsopp examined the available data in lung and also performed experiments in rats, indicating a relatively slow epithelial cell turnover, estimated to be approximately 100 d in the normal rodent tracheobronchial tree (14). Numerous studies since then have confirmed relatively slow rates of cell turnover in normal lungs, but proliferation was highly induced after injury (15)(16)(17)(18)(19)(20).…”

Basal Cells Are a Multipotent Progenitor Capable of Renewing the Bronchial Epithelium

“…Both basal and nonciliated se-cretory cell types of bronchial airways have been shown to exhibit proliferative capacity. 8,9,11,12,20,21,47 However, the relative contribution of secretory versus basal progenitor cell populations to epithelial maintenance and regeneration following injury remains controversial. Studies by Evans and colleagues 12 involving injury targeted to ciliated cells indicated that nonciliated secretory cells represent the preferred progenitor cell type of the bronchial epithelium.…”