title: Observations of development of resistance to detachment of cultured bovine bronchial epithelial cells in response to protease treatment.
abstract: Protease injury of the bronchial epithelium may play an important role in the pathogenesis of many airway diseases including asthma and chronic bronchitis. We hypothesized that neutrophil elastase can cause significant injury to the bronchial epithelium leading to detachment of bronchial epithelial cells. This detachment might be prevented if elastase is released into the airway lumen and the bronchial epithelium forms a barrier preventing access to the basal attachment sites. To assess this, the detachment of bronchial epithelial cells by elastase from extracellular matrix was measured. An increase in the resistance to detachment with time in culture was observed. The resistance to detachment was confirmed in bronchial epithelial cells, which were grown to electrically resistant monolayers on millipore filters and exposed to trypsin and elastase applied to both the apical and basal surfaces. Significantly greater detachment occurred when the proteases were applied at the basal surface versus the apical surface. Injury to the bronchial epithelium may enhance the proteolytic effect on the epithelium by disrupting epithelial barrier function. This was tested by exposing bronchial epithelial cell cultures to cigarette smoke extract before exposure to trypsin and elastase. The detachment of the bronchial epithelial cells exposed on the apical surface was increased greatly after smoke exposure. These data suggest that an intact bronchial epithelium can act as a barrier against proteolytic injury. Such a mechanism might protect the airway epithelium during intraluminal inflammation, and, if defective, might potentiate cigarette smoke-induced airway injury.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha.
authors.forename: K A
authors.initials: KA
authors.lastname: Rickard
authors.forename: J
authors.initials: J
authors.lastname: Taylor
authors.forename: S I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: D000818:Animals; D001980:Bronchi / Q000502:physiology*; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000378:metabolism; D012906:Smoke; D014357:Trypsin / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D012906:Smoke; D010196:Pancreatic Elastase; D014357:Trypsin