Expression of aminopeptidase N and dipeptidyl peptidase IV in the healthy and asthmatic bronchus.

BACKGROUND

Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and chronic inflammation of the airways. Since peptides are able to produce many of the pathophysiological features which are characteristic of asthma, peptide-mediated inflammation is thought to play a role in this disease. The effects of peptides are modulated by peptidases, which are able to degrade peptides, mostly resulting in their inactivation.

OBJECTIVES

In this study, we investigated the distribution of two peptidases, aminopeptidase N and dipeptidyl peptidase IV, in the human bronchus and determined whether their expression was altered in allergic asthmatics.

METHODS

We first determined the distribution of aminopeptidase N and dipeptidyl peptidase IV in the human bronchus using immuno- and enzymehistochemistry and compared this with the distribution of neutral endopeptidase. Secondly, the expression of aminopeptidase N and dipeptidyl peptidase IV was determined in bronchial biopsies of healthy subjects (n = 8) and allergic asthmatics (n = 12).

RESULTS

Aminopeptidase N was localized in connective tissue, blood vessels, gland ducts, perichondrium, nerves and leucocytes (mainly mononuclear phagocytes, dendritic cells, and eosinophils). Dipeptidyl peptidase IV was localized in serosal glands, blood vessels, and T cells. Immunohistochemistry and enzymehistochemistry gave similar results. Comparison of the expression of aminopeptidase N and dipeptidyl peptidase IV in bronchial biopsies of healthy controls and atopic asthmatics revealed no significant differences in the lamina propria. In contrast, in the bronchial epithelium of atopic asthmatics an increased number of aminopeptidase N-positive cells could be found. Double-staining identified these cells as L25+ dendritic cells and eosinophils.

CONCLUSIONS

We conclude that expression of aminopeptidase N and dipeptidyl peptidase IV is restricted to specific sites within the human bronchus. Furthermore, in the bronchial epithelium of allergic asthmatics an increased number of aminopeptidase N-expressing dendritic cells and eosinophils can be found.