Differentiation of tracheal epithelium during fetal lung maturation in the rhesus monkey Macaca mulatta

Abstract

Of the eight categories of epithelial cells identified in pulmonary conducting airways, four are found in the trachea of adult primates: basal, mucous goblet, intermediate, and ciliated cells. While their ultrastructure is well characterized, little is understood about their origin or differentiation. This study describes the pattern of differentiation of the tracheal luminal epithelium in a species of nonhuman primate, the rhesus monkey, Macaca mulatta. Tracheas of 57 fetal and postnatal rhesus were fixed with glutaraldehyde/paraformaldehyde: ten at 29-54 days gestational age (GA), ten at 59-80 days GA (pseudoglandular stage), sixteen at 82-130 days GA (canalicular stage), ten at 141-168 days GA (saccular stage), eight at 1-134 days postnatal, and three adults (2 yr 11 months to 11 yr 11 months). Slices taken proximal to the carina were processed for electron microscopy by a selective embedding procedure. In the youngest fetuses, essentially one population of cells lined the tracheal epithelial surface. These cells were columnar in shape with a central nucleus, few organelles, and large amounts of cytoplasmic glycogen. At 46 days GA, ciliated cells were observed on the membranous side of the trachea. Some nonciliated cells had concentrations of organelles in the most apical portion of their cytoplasm. At 59 days GA, membrane-bound cored granules were intermixed with organelles in the apices of some glycogen-filled cells. They were observed first on the cartilaginous side. Between 59 and 100 days GA, a large number of cell forms which appeared to be transitional between ciliated, secretory, basal, and undifferentiated cells were present. These included ciliated cells with electron-lucent inclusions resembling mucous granules. Mucous secretory cells were more numerous and had more granules and less glycogen in older fetuses. By 105 days GA, few of the secretory cells had significant amounts of glycogen and the cytoplasm was condensed. Secretory granules were very abundant in some cells and minimal in others. The Golgi apparatus was prominent. In animals 120 days GA and older, small mucous granule cells and basal cells resembling these cells in adults were present. By 134 days postnatal age, the epithelium resembled that in adults. We conclude that most of the differentiation of tracheal epithelium in the rhesus monkey occurs prior to birth; the cells differentiate in the following sequences: ciliated, mucous goblet, small mucous granule, basal; and basal and small mucous granule cells do not play a role in ciliated and mucous cell formation in the fetus.

Foxa2 regulates alveolarization and goblet cell hyperplasia

“…Conducting airways are lined primarily by nonciliated columnar epithelial cells (Clara cells), and by ciliated and basal cells (Plopper et al, 1986). Generally, in the mouse, goblet cells are not observed unless the animals are exposed to inflammatory stimuli, including allergens.…”

Allergen and Ozone Exacerbate Serotonin-Induced Increases in Airway Smooth Muscle Contraction in a Model of Childhood Asthma

“…Rhesus monkeys were used because they have similar lung cellular morphology, airway architecture and immunology to humans and they undergo a similar extensive period of postnatal development [35,36,37,38,39]. In addition to possessing all of the components of the intrapulmonary conducting airways that are altered in human asthmatics, rhesus monkeys display a similar progression of asthma pathophysiology and symptoms [40,41].…”

Asthma: a comparison of animal models using stereological methods

“…Epithelial differentiation (especially the secretory cell types and glandular elements) occurs post-natally for both rhesus monkeys [13,23,24] and humans [25,26]. The secretory cell population differentiates in a proximal-to-distal pattern, with nearly mature cells lining proximal airways and immature cells in more distal portions.…”

“…The expression and distribution of the cystic fibrosis transmembrane receptor [43] and keratins [44] have been characterised in airway epithelium. The pattern for differentiation of tracheobronchial epithelium [13,24,45,46] and submucosal glands has been defined [33]. While regulatory control of epithelial differentiation has been studied in vivo [19], the majority of the work has been carried out using biphasic epithelial cultures.…”