In vivo detection of a novel macrophage-derived protein involved in the regulation of nasal mucus-like glycoconjugate secretion

Background: We recently described a novel 68 kd mucus secretagogue (MMS-68) derived from human monocytes, pulmonary macrophages, and a macrophage hybridoma, clone 63. We detected MMS-68 in monocyte culture supernatants from patients with steroid-dependent asthma and in bronchoalveolar lavage fluid from patients with chronic bronchitis by antigen capture ELISA and in normal lung tissue by immunohistochemistry. Methods: To determine a role for MMS-68 in the regulation of nasal mucus, we labeled human nasal turbinates with tritiated glucosamine and assayed for the ability of the previously purified MMS-68 (stock solution) to induce mucus-like glycoconjugate release (MLGC). We also performed immunohistochemistry stains with an anti-MMS-68 antibody (1-D-10) on frozen sections (n = 5) of nasal turbinates from patients with allergic and nonallergic rhinitis who were undergoing rhinoplasty and measured MMS-68 levels in nasal lavages from patients who were undergoing topical nasal histamine or methacholine challenge. Results: MMS-68 is a potent nasal MLGC secretagogue causing a dose-dependent increase in MLGC release in vitro. Staining revealed a subepithelial distribution for MMS-68. Antigen capture ELISA of nasal lavages demonstrated mean MMS-68 levels from saline control challenge of 0.9 ± 0.5 μg MMS-68 per milligram of protein (n = 5), 8.6 ± 1.4 μg MMS-68 per milligram of protein from histamine challenge and 20.7 ± 2.3 μg MMS-68 per milligram of protein (n = 5) after methacholine challenge. Conclusion: Taken together these data suggest that MMS-68 may play a role in the normal regulation of mucus secretion.