Distribution and Number of Clara Cells in the Normal and Disturbed Development of the Human Fetal Lung

Abstract

In this study the numerical growth and topological distribution of Clara cells were investigated in normal and hypoplastic lungs of fetuses ranging in age from the 10th to the 24th gestational week. In addition, the lungs of premature infants suffering from hyaline membrane syndrome (HMS) and bronchopulmonary dysplasia (BPD) were used as a model of disturbed lung growth in the early postnatal phase. Clara cells were observed to appear in the airway epithelium of fetuses of the 15th gestational week. After the 15th week of gestation the Clara cell number increased monotonously with increasing gestational age, reaching 5.4% Clara cells in the bronchial epithelium and 11.2% in the bronchiolar epithelium at the 24th gestational week. In the investigated period of gestation the Clara cell number was significantly higher in the bronchiolar epithelium compared to the bronchial epithelium. Hypoplastic lungs showed no difference in number and distribution of Clara cells compared to normal age-matched controls. This finding suggests the growth of Clara cells to be relatively accelerated compared to the decreased maturation of the lung parenchyma. The HMS/BPD cases showed normal Clara cell counts in the bronchial epithelium, whereas in the bronchiolar epithelium this value was decreased. This finding is caused by the extreme turnover of the airway epithelium in HMS/BPD; the local distribution of the epithelial damage is speculated to be caused by the physicochemical properties of inhaled oxygen.

Amniotic Fluid Clara Cell Protein Concentration in Normal Pregnancy, a Marker of Fetal Airway Growth or Fetal Lung Maturation?

“…20 Detection of CCP in AF coincides with the appearance of Clara cells in human fetal lung, although other bronchial nonciliated epithelial cells are also capable of secreting this protein. 9,10,21 We observed a marked rise of CCP in AF before 30 to 32 weeks of gestation, which probably is a reflection of the growth of the fetal airways, of an increase in the number of cells capable of secreting CCP, and developmental changes of the expression of CCP in those cells. 9,10,22 Singh et al 23 reported similar observations in the developing rat.…”

Terminal Bronchioles Harbor a Unique Airway Stem Cell Population That Localizes to the Bronchoalveolar Duct Junction

“…[1][2][3][4][5][6][7][8] Although many studies have focused on regeneration of this tissue after injury, only recently have the intricacies of renewing such a complex epithelium begun to be elucidated. Injury models that target terminally differentiated cell populations identify the importance of the transit-amplifying (TA) subset of progenitor cells in the regeneration process.…”

Molecular Staging of Epithelial Maturation Using Secretory Cell–Specific Genes as Markers

“…In addition to steady-state heterogeneity, chronic lung diseases such as asthma, bronchopulmonary dysplasia, and chronic bronchitis cause phenotypic changes within the secretory cell population. These changes include loss of Clara cells, decreased CCSP expression, and increased production of mucus (14)(15)(16). Given the progenitor role that has been ascribed to Clara cells, the existence of multiple secretory cell subpopulations, and the phenotypic changes seen in human disease states, we sought to further characterize the molecular phenotype of airway secretory cells by expanding the available repertoire of molecular markers that can be used to follow their postnatal maturation.…”