Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps

Background: Although chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by T_H2 inflammation, the role of mast cells is poorly understood. Objective: The objective of this study was to investigate the presence, localization, and phenotype of mast cells in patients with CRS. Methods: We collected nasal tissue and nasal lavage fluid from patients with CRS and control subjects. We analyzed mRNA for the mast cell proteases tryptase, chymase, and carboxypeptidase A3 by using real-time PCR and measured mast cell protease proteins by using ELISA, immunohistochemistry, and immunofluorescence. Results: Tryptase mRNA was significantly increased in nasal polyps (NPs) from patients with CRSwNP (P <.001) compared with uncinate tissue from patients with CRS or control subjects. Tryptase protein was also elevated in NPs and in nasal lavage fluids from patients with CRSwNP. Immnohistochemistry showed increased numbers of mast cells in epithelium and glands but not within the lamina propria in NPs. The mast cells detected in the epithelium in NPs were characterized by the expression of tryptase and carboxypeptidase A3 but not chymase. Mast cells expressing all the 3 proteases were abundant within the glandular epithelium of NPs but were not found in normal glandular structures. Conclusions: Herein we demonstrated a unique localization of mast cells within the glandular epithelium of NPs and showed that mast cells in NPs have distinct phenotypes that vary by tissue location. Glandular mast cells and the diverse subsets of mast cells detected may contribute to the pathogenesis of CRSwNP.