Immunochemical localization of Clara cell protein by light and electron microscopy in conducting airways of fetal and neonatal hamster lung

Abstract

An antibody to a protein produced by Clara cells in adult Syrian golden hamsters has been used to monitor the development and functional differentiation of secretory cells in the conducting airway epithelium of this species. Lungs from fetal and neonatal hamsters at gestational day 11 and at intervals up to and including 3.5 weeks of age (as well as adults) were studied. The earliest time this Clara cell protein could be identified by immunoperoxidase labeling in the fetal conducting airways was at gestational day 15. On this day, labeling was observed in a few secretory cells lining the trachea, in many lining the lobar bronchi, and in virtually all secretory cells lining the bronchioles. Ciliated cells and endocrine cells were not labeled. Granules first appeared within the apical cytoplasm of the secretory cells on gestational day 15 at all airway levels. To identify the exact subcellular location of this protein, an ultrastructural labeling procedure using protein A gold was employed. The gold particles labeled only electron-dense granules within the secretory cells, indicating that they represent the specific site of this protein. Since secretory cells in the most distal conducting airways began to produce this protein on the same day in development as cells in the larger airways, including the trachea, this expression of functional maturation occurs simultaneously throughout the conducting respiratory tree rather than proceeding sequentially in a cranial to caudal direction. Consequently, secretory cells lining the smaller conducting airways mature more rapidly than those lining the larger airways.

Clara Cell Protein in Human Amniotic Fluid: A Potential Marker of Fetal Lung Growth

“…The average increase was only 3.8-fold in amniotic fluid but reached 30-fold in the lung, which is comparable to the factor of 25 observed in the present study for amniotic fluid. In hamsters, too, CC16 was immunolocalized by electron and light microscopy in the fetal lung from d 15 of gestation, and an increasing amount of labeling was noted until birth and during the first few weeks after birth (16).…”

Ontogeny of Clara cell-specific protein and its mRNA: their association with neuroepithelial bodies in human fetal lung and in bronchopulmonary dysplasia.

“…In RNA blot analysis of developing rat lung, CCSP gene expression is not confined to the lung but is also seen in the trachea (Hackett et al, 1992). In Syrian golden hamsters, CCSP immunoreactivity and mRNA have been observed in secretory cells of the trachea, bronchi, and bronchioles (Strum et al, 1990(Strum et al, , 1992. liken together, these data indicate that the CCSP gene is expressed not only in bronchiolar Clara cells but also in nonciliated cells of the trachea and bronchi in several mammalian species, including those of humans, at various stages of development.…”

“…These data suggest that Clara cell cytodifferentiation occurs early during human lung development. Compared with human lung, CCSP expression and mRNA appear relatively late in fetal life in the lungs of several mammals studied, with most of the expression appearing postnatally (Cardoso et al, 1993;Ten Have-Opbroek and De Vries, 1993;Hackett et al, 1992;Strum et al, 1990). Differentiation of bronchial epithelium and CCSP expression in the mouse have been shown to be coincident with the loss of SP-C expression in bronchi, which is now expressed in distal respiratory epithelium (Wert et al, 1993).…”

Morphometric analysis of the immunohistochemical expression of Clara cell 10-kDa protein and surfactant apoproteins A and B in the developing bronchi and bronchioles of human fetuses and neonates

“…They are also involved in pathobiological conditions, including malignant transformation, leading to the development of peripheral lung adenocarcinoma and in the inflammatory repair process at the critical junction between the conducting airways and the alveoli [6,10,27,35]. Their role in developing lungs remains to be clarified [8,12,18,32,39].…”