Secretory leukoprotease inhibitor (SLPI) is a secreted glandular protein thought to regulate elastase activity and, more recently, to inhibit both mast cell chymase activity and histamine release from mast cells. To begin to examine the possible role of SLPI in humans, we determined the distribution of SLPI in the human nasal mucosa and quantitated the functional activity of SLPI in nasal lavage fluid. Immunochemical staining of the nasal mucosa revealed intense, selective immunoreactivity in the serous cells of the submucosal glands. The level of SLPI in nasal secretions was measured by enzyme immunoassay. In control subjects (n= 8), the level of SLPI in nasal lavage fluid (NLF) after saline challenge (baseline level) was 2.5±0.5 tlg/ml, accounting for 3.3±0.6% of total protein in nasal secretions. After methacholine (MCh) and histamine (HIST) challenge, the level of SLPI increased to 7.0±1.4 and 6.1±1.6 tlg/ml, respectively (both p< 0.05). In atopic patients (n= 8), the level of SLPI after MCh and HIST challenge increased from a baseline level of 7.6±2.0 tl9/ml to 22.1±6.4 and 25.2±10.5tlg/ml, respectively. After allergen challenge, the concentration of SLPI increased significantly in atopic patients, whereas there was no increase in the level of SLPI in control subjects. Western blot analysis of MCh-induced nasal secretions revealed a single band with a molecular weight of 12 kO, the same as recombinant SLPI. Functionally active SLPI (inhibition of neutrophil elastase activity) in nasal lavage fluid (NLF) was 220.9±31.4 nM, and approximately 970/0 of anti-HNE (human neutrophil elastase) capacity found in NLF was due to SLPI. These results indicate that SLPI is selectively present in large quantities in serous cells in the nasal mucosa and that it constitutes a significant portion of the total protein in nasal secretions. SLPI is secreted on challenge not only with MCh or HIST but also, in atopic patients, with allergen, and it likely helps regulate inflammatory protease activity on the mucosal surface.

Secretory leukoprotease inhibitor (SLPI) is a 12-kOserine protease inhibitor produced locally by the cells of the human airway mucosa. The principal physiologic role of SLPI is to provide protection of the epithelial surface against human neutrophil elastase (HNE), an enzyme that can cause epithelial damage (1). In addition, SLPI also inhibits mast cell chymase (2), one of the major proteases released during degranulation. Chymase is one of the mast-cellderived glandular secretagogues (3). It was recently reported that SLPI and other antichymotryptic-type inhibitors can inhibit histamine release from mast cells in vitro (4). Although it has been observed that SLPI is present in the airways (5, 6), its function is not well understood, and it is not clear whether it provides functional anti-HNE protection for the nasal epithelial surface. In order to further characterize SLPI in human in vivo, we studied the distribution of SLPI in the human nasal mucosa. The secretion of SLPI from human subjects was examined in response to