Cellular sequence of tracheal repair in sheep after smoke inhalation injury

Abstract

The cellular repair process of injured tracheal epithelium is described for sheep after exposure to toxic smoke containing high concentrations of acrolein. Fourteen fasted 3-4-year-old ewes had a portion of their cervical trachea exposed to cotton smoke for 20 min and then were sacrificed at various time intervals ranging from 1 to 22 days after exposure. Within 1 day of injury, columnar epithelium sloughed intact from the trachea with a concomitant reduction of nearly 35% in the basal cell population. At 2 days of recovery, the cellularity of the epithelium had increased and mitotic figures were observed in some tracheal epithelial and gland cells. By 8 days, undifferentiated hyperplastic cells increased to 30/100 microns, differentiated nonciliated columnar cells first appeared, and the basal cell population returned to a normal count of 13 cells/100 microns. Thirteen days after exposure, the undifferentiated hyperplastic cell population had declined to 7 cells/100 microns, nonciliated columnar cells were at control values, and some ciliated cells were identified. At 18 and 22 days, epithelium was normal in appearance and the count was 13 cells/100 microns. Data suggest that because the columnar epithelium sloughs intact with the cilia remaining active, toxic smoke may affect their attachment to the basal lamina. Furthermore, the regeneration process involves differentiation of hyperplastic cells in which they elongate down to the basal lamina, thus re-establishing the integrity of tall epithelium in the sheep trachea.

Growth factors accelerate epithelial repair in sheep trachea

“…In previous studies on smokeinduced tracheal injury, we found that in many large areas columnar cells had sloughed off, leaving the basal lamina covered only by a single layer of flattened basal cells [3]. The lamina propria of the tracheal mucosa showed marked congestion and edema with numerous inflammatory cells.…”

“…An increase in edema formation in the injured tracheal segment was also noted, as evidence by a five to sevenfold elevation in lymphatic drainage, hyperemia, and a significant increase in wet-to-dry weight ratios [1]. The repair of the injured site is characterized initially by proliferation of surviving cells [3,6,10]. Some are nonciliated columnar cells at the edge of the injured area that spread inward and begin to proliferate.…”

“…The isolated segment of trachea was exposed to cotton smoke for 20 rain. Cotton smoke, cooled to 37°C to prevent thermal injury, was previously shown to cause sloughing of exposed epithelium down to and including nearly 50% of the basal cells within the first day after exposure [3]. Twelve injured sheep were treated serially with an aerosol of platelet derived growth factor and epidermal growth factor beginning 72 h after injury.…”

“…Airway injury from exposure to noxious smokes, fumes, and gases [I, 3,10] can range from totally reversible, where the cells return to normal after the irritant is removed, to exfoliation and desquamation of cells, including basal cells. In general, toxic agents exert their damaging effects by direct action on the cell membrane, immunologic mediators, or metabolic pathways.…”

“…The repair process involves proliferation and migration of surviving nonciliated cells and differentiation to the normal phenotype. Cellular repair in the trachea of sheep after toxic smoke injury has been previously described [3], however, no attempt was made to modulate the repair process. In the present study, growth factors were used to accelerate repair in an injured segment of the cervical trachea of sheep.…”