Am. J. Respir. Cell Mol. Biol., Vol 13, No. 2, 08 1995, 144-151.
Clara cell heterogeneity in differentiation: correlation with proliferation, ultrastructural composition, and cell position in the rat bronchiole
CM Ji, CG Plopper and KE Pinkerton
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, USA.
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.
