1977). They likely differentiate into other cell types , and could function 
as a "stem" cell for other airway columnar cells (see below) . 
Basal cells - these are ovid or pyramidal shaped cells scattered along the 
basement membrane throughout the airways, although more frequently in large 
bronchi. In bronchioles, basal cells represent <202 of the epithelial cells 
(Danel et al . , 1992; Jeffrey and Reid, 1975). The nucleus fills most of the 
cell; there are no secretory granules, but some RER and Golgi. Basal cells 
have a broad based surface on the basement membrane to which they are 
tightly attached by hemidesmosomes (Kawanami et al . , 1979). 
Clara cells - this is a columnar cell with an apical surface bulging into 
the airway lumen. Clara cells are confined to the bronchioles, and are 
sometimes referred to as "nonciliated bronchiolar epithelial cells" 
(Massaro, 1989). The Clara granules do not coalesce. These cells are be- 
lieved to contribute significantly to bronchiolar secretions. 
1.9.3 Normal Epithelial Cytokinetics 
In the normal lung, the airway epithelium constantly turns over, but at a 
slow rate (Breeze and Wheeldon, 1977; Evans and Shami , 1989). Most data is 
from experimental animals and it varies by species (Frasca et al., 1968). 
Mitoses are rarely seen (Breeze and Wheeldon, 1977). At any given moment, 
approximately 1 of 200 cells are synthesizing DNA (Greisin, 1977) . Esti- 
mates of complete cell turnover (100% of the epithelial cells replaced) in 
the bronchi of experimental animals vary from 7 to 21 days up to 82 to 131 
days (Blenkinsopp , 1967; Shorter et al . , 1964; Spencer and Shorter, 1962). 
Cell turnover is more rapid in larger airways with estimates of up to 3- 
fold in large compared to small bronchi (Bolduc and Reid, 1967) . There is 
no quantitative data relating to epithelial cell turnover in the human 
lung. 
The classic concept of airway epithelial cell ontogeny held that the basal 
cell was the stem cell for all of the major airway epithelial cells (Evans 
and Shami, 1989). This view has been modified somewhat to the concept that 
basal cells regenerate themselves and likely some columnar cells, but that 
non-ciliated columnar cells can also regenerate columnar cells. In this 
regard, while ciliated cells are considered to be terminally differentiat- 
ed, mucus, serous, undifferentiated, and Clara are all capable of replica- 
tion. In the bronchioles, Clara cells likely serve as the progenitor for 
other Clara cells and ciliated cells. In the submucosal glands, the progen- 
itor cells are not clear. It has been hypothesized that the undifferentiat- 
ed columnar cells are the progenitor for Goblet and serous cells but this 
is not proven. In response to injury, all of the non-ciliated columnar 
cells undergo division, on the average they spend 8-12 hours in S phase, 2- 
3.5 hours in G2 and 0.6 hour in M (Boren and Paradise, 1978). 
1.9.4 Epithelial Lining Fluid, Pericellular Fluid and Mucus 
The surface of the airway epithelium is covered with epithelial lining 
fluid (ELF) that is 8 to 16 nm thick in the large airways. In the bronchi, 
electron microscopic observations demonstrate the airway ELF consists of 
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Recombinant DNA Research, Volume 16 
