ENHANCED EXPRESSION OF NEUTRAL ENDOPEPTIDASE (NEP) IN AIRWAY EPITHELIUM IN BIOPSIES FROM STEROID-TREATED VERSUS NONSTEROID-TREATED PATIENTSWITH ATOPIC ASTHMA

The expression of the endogenous neuropeptide-degrading enzyme, neutra l endopeptidase (NEP; CALLA, CD10, E.C.3.4.24.11) on cultured human ai rway epithelial cells can be upregulated by corticosteroids. We examin ed whether NEP expression in the airway epithelium or lamina propria i n bronchial biopsies is enhanced in atopic asthmatics on regular inhal ed steroids as compared with those without steroid treatment. Forty no nsmoking adults (age 19 to 48 yr) with mild to moderate asthma (forced expiratory volume in 1 s greater than or equal to 50 % pred., histami ne PC20 range 0.02 to 7.6 mg/ml) with (n = 23) or without (n = 17) reg ular inhaled steroids treatment entered the study. Biopsies were taken at (sub)segmental level from the right lower lobe, the middle lobe, a nd the main carina. Immunohistochemical staining was performed on cryo stat sections using the VIL-A1 monoclonal antibody against CD10 (NEP). Intra- and inter-observer repeatability of a semiquantitative scoring method was good as assessed by weighted kappa (kappa(w) ranging from 0.66 to 0.81). In the airway epithelium, NEP-positive sites were withi n the basal layer and, in contrast with studies applying other antibod ies, also at apical sites and within the lamina propria. In both the e pithelium and lamina propria, NEP expression was not significantly dif ferent between the three biopsy sites (Friedman's nonparametric two-wa y analysis of variance; P > 0.68), nor was expression in the lamina pr opria associated with inhaled steroid usage (Mann-Whitney U test; P = 0.98). However, NEP expression was significantly enhanced in the airwa y epithelium in patients using inhaled steroids as compared with nonst eroid users (mean rank: 23.4 and 15.5, respectively; P = 0.02). Among nonsteroid-using subjects, NEP expression was related to symptoms and the methacholine PC20 (R-s: -0.69 and 0.49, respectively; P less than or equal to 0.04). We conclude that the expression of NEP is enhanced in airway epithelium in bronchial biopsy specimens from patients with atopic asthma who are regularly using inhaled steroids as compared wit h patients who do not. This fits the hypothesis that the anti-inflamma tory effect of corticosteroids within the airways is partially mediate d by the upregulation of the endogenous neuropeptide-degrading enzyme NEP.