Postnatal Development of Tracheal Surface Epithelium and Submucosal Glands in the Ferret

Abstract

We explored the usefulness of the postnatal ferret as a model for early developmental events in the large airways, using light and scanning electron microscopy. In the first 28 postnatal days, ferret tracheal surface epithelium and glands undergo dramatic growth and development. Tracheal surface area increases 8-fold. At birth, ciliated cells are sparse (9.4 +/- 1.2% of total epithelial cells). A significant increase in ciliated cells is observed at weekly intervals and by day 28 the ciliated cell is the predominant cell type (54.2 +/- 2.8% of total epithelial cells). Secretory cells decrease from 66.4 +/- 1.0% at birth to 22.2 +/- 2.8% of total epithelial cells. Histochemical staining of the granules of the epithelial secretory cells changes from predominantly non-acidic (staining with PAS but not Alcian blue) to predominantly acidic (staining also with Alcian blue). During the same time interval, tracheal glands develop from intraepithelial cellular aggregates devoid of secretory granules at birth into complex, submucosal tubuloacinar structures composed predominantly of cells containing non-acidic secretory granules at 28 days. Therefore, infant ferrets offer an opportunity to examine the structural and functional components of the mucociliary clearance mechanism at developmental stages which occur prenatally in many laboratory animals and in humans.

Newborn Cystic Fibrosis Pigs Have a Blunted Early Response to an Inflammatory Stimulus

“…It is possible that these differences between the pig and ferret models reflect species-dependent differences in the development and regulation of airway innate immunity. Note that in contrast to humans and pigs, ferrets have few ciliated airway epithelia and no submucosal glands at birth (45). Alternatively, methodologic differences in how and when the tissues were sampled and/or analyzed may have contributed to the differing results.…”

Lysozyme Secretion by Submucosal Glands Protects the Airway from Bacterial Infection

“…Unlike mice, ferret cartilaginous airways have similar airway cell types and abundance of SMGs as seen in humans (17,20). Xenograft airways without SMGs were generated from isolated adult ferret tracheal airway epithelial cells that were grafted onto canulated denuded rat tracheal subcutaneous implants of nu/nu mice.…”

The Glandular Stem/Progenitor Cell Niche in Airway Development and Repair

“…Unlike mice, ferrets and humans share a remarkably similar proximal airway cytoarchitecture (11)(12)(13). As in humans, SMGs in the ferret are distributed throughout the cartilaginous airways (12,14).…”

“…In humans, airway SMG development initiates when clusters of surface epithelial cells invade the lamina propria of the proximal trachea during gestation (14). In ferrets, by contrast, SMG development initiates within the trachea during the first few postnatal weeks of life, a point at which this structure closely resembles the in utero human airway at gestation stages (12,14). Although the ferret is the only known placental mammal in which substantial development of both the airway epithelium and SMGs occur postnatally, these morphologic and developmental features of the ferret airway make it uniquely suited to serve as a model for studies pertaining to the development of tracheal SMGs.…”