CLARA CELL-DIFFERENTIATION IN THE MOUSE - ULTRASTRUCTURAL MORPHOLOGY AND CYTOCHEMISTRY FOR SURFACTANT PROTEIN-A AND CLARA CELL 10 KD PROTEIN

The morphologic and functional differentiation of the nonciliated colu mnar (Clara) cell, one of two secretory cell types in distal most bron chioles in mammals, was studied in the mouse. Lungs from embryos (16-1 9 days of developmental age, dDA; birth on day 19), postnatal animals (5-20 days postnatally dPN), and adult animals were investigated by tr ansmission electron microscopy, using standard staining procedures and immunogold (GAR-Au10) labeling for SP-A and Clara cell 10 kD antigen (CCA). At 16 dDa, all the columnar epithelial cells lining prospective distalmost bronchioles lacked distinctive features. By 17 dDa, some c ells displayed a few cilia or apical dense granules. At 18 dDa, many n onciliated columnar cells had apical protrusions, as are seen in adult Clara cells. Apical concentrations of glycogen observed in nonciliate d columnar cells perinatally were absent by 5 dPN, whereas apical dens e granules became more abundant. Profiles of smooth and rough endoplas mic reticulum (ER), which had been randomly distributed, exhibited a s elective, adult distribution at 20 dPN (apical vs. basal cytoplasmic d omains). Labeling for SP-A and CCA, which was almost absent between 17 and 19 dDa, reached adult levels at the same time. The two proteins d iffered in distribution. SP-A predominated in. adluminal cytoplasmic a reas, where it was found over dense granules, vesicles, and multivesic ular bodies; it was also present in bronchiolar lumens and intercellul ar spaces but not in rough ER or Golgi apparatus. In contrast, CCA sho wed a more uniform distribution; it was present over the same structur es as SP-A and in the synthetic organelles. Ciliated columnar cells we re virtually devoid of SP-A and CCA. We conclude that mouse Clara cell s acquire a mature phenotype by 20 dPN. They are likely to be involved in recycling and/or degradation of SP-A that is internalized from air way lumens through their apical or lateral cell borders; furthermore, they synthesize the Clara cell 10 kD protein. These two Clara cell fun ctions (first detectable late prenatally) reach mature levels by 20 dP N. (C) 1993 Wiley-Liss, Inc.