Secretion and gene expression of secretory leukocyte protease inhibitor byhuman airway submucosal glands

Submucosal glands were isolated within 4 h of death from tracheae and bronc hi obtained from autopsied lungs, and the secretory response of secretory l eukocyte protease inhibitor (SLPI) was examined with ELISA and a secretory index. Although human neutrophil elastase (HNE) at low concentrations incre ased SLPI secretion above the control level (i.e., 149% of control level at 10(-11) M), HNE at high concentrations significantly decreased it below th e control level (i.e., 16% of control level at 10(-7) M). The decrease in S LPI concentration was shown to result from the degradation of SLPI by exces sive HNE. Methacholine induced significant secretion (i.e., 363% of control level at 10(-5) M) that was abolished by both M-1 and M-3 receptor antagon ists. A semiquantitative analysis of SLPI mRNA by RT-PCR and Southern blot showed that compared with the superficial epithelium, submucosal glands had a 30-fold or higher level of SLPI mRNA. Both HNE and methacholine signific antly increased the level of SLPI mRNA in submucosal glands in a dose-depen dent manner (i.e., 357% of control level at 10(-7) M and 175% of control le vel at 10(-5) M, respectively). These findings indicate that human airway s ubmucosal glands can transcribe 30-fold or more SLPI mRNA than the superfic ial epithelium and that SLPI mRNA transcription and secretion are regulated by both HNE and muscarinic receptors.