Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema.

Abstract

A B S T R A C T A single intratraclheal instillation of pancreatic elastase in hamsters indtuces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchiial epithelitum of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, prodtuced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P < 0.005) than that of tunexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear btut the possibility is raised that the bronchial changes may be dtue to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, uinder appropriate circu-mstances, a single puilmonary insult in man could lead to a permanent luing injtury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.

Immunocytochemical evidence for extra-cellular initiation of elastase-induced bronchial secretory cell metaplasia in hamsters

“…In addition to elastin, HNE can degrade other structural components in this region, including collagen types I-IV, laminin, fibronectin and proteoglycans [24,47,48]. Proteolytic degradation of extracellular matrix involved in epithelial attachment may explain the epithelial desquamation seen focally in hamster lungs exposed to elastase in vivo [1], and the detachment of epithelial cells from elastase-treated human respiratory mucosal biopsies in vitro [49].…”

“…Hamsters exposed to an intratracheal instillation of the broad-spectrum, proteolytic enzyme, elastase, develop bronchial secretory cell metaplasia over a period of several weeks [1][2][3][4][5]. This epithelial alteration manifests microscopically as a cytoplasmic accumulation of mucin granules with an overlying luminal layer of mucus.…”

The role of airway mucus in pulmonary toxicology.

“…A study by Christensen et al (171) showed that a single dose of pancreatic elastase causes an apparently irreversible goblet cell metaplasia in guinea pigs. In a more recent study, the steroidal anti-inflammatory drug dexamethasone was effective in inhibiting neutrophil elastase-induced goblet cell hyperplasia in rat trachea, suggesting the involvement of lipid mediators (127).…”

A comparison between the epithelial tight junction morphology of human extrapulmonary bronchi and rat trachea

“…Studies on rodents have played a major part in advancing our understanding of the structure and function of normal mammalian airways [1], and nonprimate animal models have been successfully developed for the investigation of the pathogenesis of airway disease [2][3][4][5][6][7][8]. The specific pathogen-free rat, following exposure to a variety of inhaled irritants, has been widely used to model human chronic bronchitis: the response to irritation includes a thickening of airway epithelium, goblet cell hyperplasia, increased production of mucus and increased epithelial permeability [4,[9][10][11].…”