ULTRASTRUCTURE OF THE TRACHEAL, BRONCHIAL, AND BRONCHIOLAR EPITHELIUM
The lining of the respiratory airways is
predominantly a pseudostratified, ciliated, columnar epithelium in which all
cells are attached to the basement membrane but not all reach the lumen. In the
smaller peripheral airways, the epithelium may be only a single layer thick and
cuboidal rather than columnar because basal cells are absent at this level.
Ciliated cells are present in even the
smallest airways and respiratory bronchioles, where they are adjacent to
alveolar lining cells. The “ciliary escalator” starts at the most distal point
of the airway epithelium. In smaller airways, the cilia are not as tall as in
the more central airways. Eight epithelial cell types can be identified in
humans, although ultrastructural features and cell kinetics have been studied
mainly in animals. The following classification is based on studies in the
rat: the (1) basal and (2) pulmonary neuroendocrine cells are attached to the
basement membrane but do not reach the lumen; (3) the intermediate cell is
probably the precursor that differentiates into (4) the ciliated cell, (5) the
brush cell, or one of the secretory cells (6) the mucous (goblet) cell, (7) the
serous cell, or (8) the Clara cell.
The basal cell divides and
daughter cells pass to the superficial layer.
The pulmonary neuroendocrine cell
(PNEC), previously referred to as the Kulchitsky cell, contains numerous
neurosecretory granules and is a rare, but likely important, functional cell of
the airway epithelium. The PNEC neurosecretory granules contain serotonin and
other bioactive peptides such as gastrin-releasing peptide (GRP). PNECs are
more numerous before birth and may play a role in the innate immune system. The
intermediate cell is columnar. It has electronlucent cytoplasm and no special
features. It is probably the cell that differentiates into the others.
The ciliated cell carries the
cilia of the respiratory epithelium. The cilium has nine double pairs of
axonemes and a special axoneme in the center. The arrangement is modified at the
base and at the apex, where a coronet of small claws has been identified. The
feet of the axonemes are arranged so that a cilium “plugs” into the cytoplasm.
The axonemes are attached to each other by “arms” of dynein, a contractile
protein, and these provide the mechanism for ciliary motion.
The brush cell resembles a
similar cell type found in the gut and in the nasal sinuses. Its function in
the respiratory tract remains unknown, but hypotheses regarding its function
include immune surveillance, cell regeneration, chemoreceptor, sensor of
alveolar fluid or air tension, and regulator of capillary resistance and
perfusion.
The mucous (goblet) cell is a
secretory cell containing numerous large and confluent secretory granules.
Electron microscopic studies have shown that confluence represents fusion of the
two trilaminar membranes of adjacent granules to produce a pentilaminar layer.
The serous cell resembles the
serous cell of the submucosal gland and contains small, discrete, electrondense
secretory granules. Its cytoplasm is also more electron dense than that of the
Clara cell.
The Clara cell also contains
small, discrete, electrondense granules, but compared with the serous cell, the
cytoplasm is electron lucent, and there is relatively more smooth than rough
endoplasmic reticulum.
The serous cell is mainly found
centrally; the Clara cell is found only distally. These are the more common
secretory cells of the airways, but irritation, drug reaction, or infection may
lead to an increase in the number of secretory cells. The serous and Clara
cells then develop into mucous cells. Differentiated cells are seen in mitosis,
but this is probably not the main way that cell numbers increase.
The basement membrane is well defined
and becomes thinner in small airways. In certain diseases notably asthma the
reticular basement membrane (lamina reticularis) increases in thickness,
although its structure remains normal.
Nerve fibers are seen within the
epithelium. They are nonmyelinated and without a Schwann cell sheath. Their
vesicle content suggests that the fibers are sensory or motor and either
cholinergic or adrenergic in type.
