Decreased expression of angiotensin-converting enzyme in the airway epithelium of asthmatic subjects is associated with eosinophil inflammation.

摘要

BACKGROUND: Angiotensin-converting enzyme (ACE) is a peptidase involved in the metabolism of several bioactive peptides. It may be involved in the airway inflammation and hyperresponsiveness that occur in asthma. OBJECTIVE: We studied the expression of ACE in the airway mucosa of normal and asthmatic subjects and assessed the relationship between ACE expression and airway inflammation and bronchial hyperresponsiveness in asthma. METHODS: We used immunohistochemistry to study the ACE expression and airway inflammation in bronchial biopsy samples obtained by fiberoptic bronchoscopy from 20 asthmatic subjects randomly assigned to groups treated with (n = 10) or without inhaled corticosteroids (n = 10) and from normal subjects (n = 10). Airway response to methacholine and bradykinin was also determined for all subjects. RESULTS: In normal subjects ACE was present in the surface epithelium, the endothelial cells of the lamina propria, and the submucosal glands, in which ACE was found in seromucous cells and in secreted mucus. ACE was not detected in smooth muscle cells and in most of the endothelial cells of the vascular network surrounding the glands. ACE was absent or present at lower levels in the surface epithelium of asthmatic subjects not treated with corticosteroids compared with those treated with corticosteroids and the control group. In asthmatic subjects low levels of ACE in the epithelium were associated with larger numbers of eosinophils in the epithelium and lamina propria. There was no relationship between ACE levels in the airway mucosa and airway responsiveness to methacholine and bradykinin. CONCLUSION: ACE expression is decreased in the epithelium of asthmatic patients and is associated with increased eosinophil inflammation.