Thomas F. Boat

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

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.

Epithelial cell dysfunction in cystic fibrosis: implications for airways disease.

An important pathophysiologic factor in CF airways is the failure to clear poorly hydrated secretions. The water deficit in CF mucous secretions can now be ascribed to a fundamental defect of epithelial cell regulatory processes which promotes sodium reabsorption from surface liquids and interferes with chloride secretion onto the luminal surface. In addition, it is now known that CF airway epithelial cells oversulfate high molecular weight glycoconjugates, both secreted and cell surface‐associated. Oversulfation of glycoconjugates may contribute to the altered clearance properties of CF airways mucus and in addition could favor colonization of airways by organisms such as P. aeruginosa.

Differential effects of ozone on lung epithelial lining fluid volume and protein content

Urea dilution has been used to estimate the volume of epithelial lining fluid (ELF) in the respiratory tract. However, ELF volume may be overestimated as the result of rapid net diffusion of urea from tissues into the bronchoalveolar lavage (BAL) fluid. This study established a protocol for rat BAL in a manner that minimizes this problem and then used this procedure to examine the edemagenic effects of ozone (O3) exposure on ELF volume and the concentrations of ELF protein and albumin. One passage lavage with variable dwell times up to 30 s showed no difference in recovered urea, protein, and albumin and ELF volume between 0 and 4 s, but a progressive increase of each thereafter. The calculated concentrations of protein and albumin in ELF did not vary significantly with dwell time. By increasing the number of lavage passages from one to three, the amounts of recovered urea, protein, and albumin and estimated ELF volume were increased with each passage. Again, the calculated concentrations of protein and albumin in ELF did not vary appreciably. When a single lavage passage and no added dwell time were used, it was observed that exposure of rats to 2 but not 0.5 and 1 ppm O3 increased urea, protein, and albumin in the BAL immediately after 6 h exposure. In addition, at 18 h postexposure to 1 ppm O3, ELF volume increased only 21%, but protein and albumin concentrations in ELF were 2.3- and 4.5-fold of control values, respectively. A higher O3 concentration (2 ppm) moderately increased ELF volume (+83%) and exerted even greater effects on concentrations of ELF protein (7.8-fold) and albumin (19-fold) while lower O3 dosage (0.5 ppm) had no significant effect. SDS-PAGE analysis showed that small serum proteins including albumin were greatly enriched in lung BAL fluid of 1 ppm O3-exposed rats. These results demonstrate that movement of water and protein into the airspaces after O3 exposure is not strictly coupled, and that protein recovery by BAL should cautiously be used to indicate airspace edema as a result of O3 injury.

Ciliary dysmorphology and dysfunction - Primary or acquired?

Cilia at the epithelial surface of conducting airways protect the lungs through their pivotal role in the clearance of mucus and potentially injurious inhaled particles. Clearance requires ciliary ...

Features of Developing Ferret Tracheal Epithelium: Ultrastructural Observations of in Vivo and in Vitro Differentiation of Ciliated Cells

Ultrastructural features of the developing, surface epithelium of ferrets from birth to 28 days of age were characterized. Progressive ciliogenesis in vivo was observed, beginning with cells covering the membranous portion of the trachea. Emerging cilia appeared in ultrathin sections and by scanning electron microscopy at sites correlating with accumulation of integral membrane particles seen in freeze-fracture preparations. Two patterns of ciliogenesis were observed: (1) the random emergence of cilia over the apical cell surface, and (2) initial emergence of cilia at the peripheral boundary of the luminal border of individual cells. Novel, ringlike structures were observed on the surfaces of nonciliated cells at all ages studied. Active ciliogenesis as well as the appearance of ring structures also were documented in the superficial epithelium from 1- to 5-day-old animals maintained in vitro for up to 4 days.

Cystic fibrosis: Overview

Cystic Fibrosis (CF) is one of the most common familial recessive diseases. Prevalence varies with ethnicity and is especially high in Caucasians, affecting about 1 in 2000 to 1 in 4000 live births (for review, see 1-3). In Hispanic Americans, African Americans, and Asian Americans, the disorder is less prevalent (1 in 9200, 1 in 15,000, and 1 in 31,000, respectively) (1-3). CF is a multisystem disease, affecting the respiratory, digestive, and male reproductive systems (13). Pulmonary disease is the major cause of morbidity and mortality, with chronic lower airway infection and inflammation leading to bronchiectasis and, eventually, to extensive airway damage and fibrosis of lung parenchyma (1,2). Disease severity can range from infertility (in males) without any pulmonary manifestations to recurrent sinusitis and bronchitis with onset in young adulthood to severe lung, pancreatic, and liver disease with onset in infancy. The great majority of CF patients suffer from pancreatic insufficiency, and more than 95% of males with CF are infertile, due to azoospermia secondary to agenesis of Wolffian duct structures (1,2). Some affected individuals demonstrate pancreatic sufficiency, which is correlated with a milder clinical course and increased survival (nonclassic CF) (1,2). Early diagnosis of CF is important, since it can help to prevent malnutrition and failure to thrive in infants and children through pancreatic enzyme replacement and chronic bacterial airway infection through antibiotic prophylaxis.