Accession Number : ADA336938

Title :   Acute Airway Injury and Response: Combined Effect of Smoke and Combustion Products on Mucin Gene Expression and Regulated Mucin Production in the Tracheal-Bronchial Epithelium (CIC3).

Descriptive Note : Final rept. 1 Jul 95-31 Dec 97.

Corporate Author : WILLIAM BEAUMONT ARMY MEDICAL CENTER ELPASO TX

Personal Author(s) : Bhattacharyya, Sambhu

PDF Url : ADA336938

Report Date : DEC 1997

Pagination or Media Count : 32

Abstract : Rabbit tracheal explants, exposed to burning pine wood smoke, were cultured in a chemically defined medium with and without retinoic acid(+/-RA). 15-20 minute exposures led to a RA-independent degeneration of the mucocilitary epithelial sheath. In 10 minute exposures tissue integrity was retained, but epithelial morphology changed from normal pseudostratified columnar to the flattened appearance typical of the squamous phenotype. Despite the dramatic shift in morphology, explants exhibited normal RA-dependent mucin gene expression characteristic of the mucociliary phenotype Furthermore, electron micrographs showed continued presence of both secretory granules and cilia. RA(+) cultures also showed a normal pattern of adherent epithelial cells. In RA(-) cultures, however, there were prominent intercellular spaces indicating an RA dependence for maintaining adhesive contacts following smoke exposure. An 18-mer mucin antisense oligomer that suppressed mucin gene expression and secretion also unexpectedly blocked the smoke induced metaplasia in RA(+) cultures, but the sense oligomer had no effect. This study demonstrates that combined therapy of retinoids and antisense oligomer may have potential clinical implication the treatment of people, including combat soldiers, exposed to smoke.

Descriptors :   *EPITHELIUM, *TOXICITY, *SMOKE, *GENES, *WOUNDS AND INJURIES, *TRACHOMA, *COMBUSTION PRODUCTS, *BRONCHITIS, *MUCIN, WARFARE, PRODUCTION, EXPOSURE(GENERAL), ARMY PERSONNEL, MORPHOLOGY, ELECTRON MICROSCOPY, PATTERNS, THERAPY, CELLS(BIOLOGY), SUPPRESSION, WOOD, RABBITS, SECRETION, GRANULES, VITAMIN A, CILIA.

Subject Categories : Medicine and Medical Research
      Toxicology
      Environmental Health and Safety

Distribution Statement : APPROVED FOR PUBLIC RELEASE