Reversible pancreatic elastase-induced bronchial secretory cell metaplasia in the rat

Abstract

Porcine pancreatic elastase (PPE) causes irreversible secretory cell metaplasia (SCM) in the intrapulmonary bronchi of hamsters. To determine whether this lesion can be induced in another rodent species, PPE was transorally instilled into the lungs of anesthetized rats. Saline-treated rats served as controls. Animals were killed 1 week, 3 weeks and 3 months after enzyme treatment and the lungs were inflation-fixed with 4% formalin/1% glutaraldehyde in 0.1 M Na cacodylate buffer at pH 7.4. Transverse sections from 3 intrapulmonary airway levels were embedded in paraffin and in glycol methacrylate. The secretory cell index (SCI) was determined from PAS-stained paraffin sections using a standardized scale of 0 to 4. There were no significant differences between SCI values of PPE-treated rats and saline-treated controls at any time point. Secretory cells in methacrylate sections were subclassified into S₁, S₂ and S₃ cells on the basis of increasing amounts of PAS-positive intracellular granules. At one week, there was no effect of PPE on airway level I secretory cells, but significant increases in numbers of S₂ and S₃ cells were seen in level II and in S₃ cells in level III. At 3 weeks, the number of S₁ cells were increased in level I and S₂ and S₃ cells were increased in level III; level II secretory cells were unaffected. Level III secretory cells had returned to normal by 3 months. There were no significant differences between treatment groups in the total number of secretory cells (S₁ + S₂ + S₃) at any airway level or time point examined. We conclude that a single intratracheal instillation of PPE causes mild SCM in rat intrapulmonary bronchi; recovery is complete by 3 months.