Age-related Reduction Of S100A8/A9 In Chronic Rhinosinusitis Is Associated With Increased Production Of Soluble gp130

Abstract

S A T U R D A Y 163 Mast Cells with a Unique Phenotype Are Highly Elevated in Chronic Rhinosinusitis with Nasal Polyps T. Takabayashi, A. Kato, A. T. Peter, L. A. Suh, R. Carter, J. Norton, L. C. Grammer, B. K. Tan, R. K. Chandra, D. B. Conley, R. C. Kern, S. Fujieda, R. P. Schleimer; The Division of Allergy and Immunology Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, The Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, University of Fukui, Fukui, JAPAN, Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Although chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by Th2 inflammation, the role of mast cells is poorly understood. The objective of this study was to investigate the presence, localization and phenotype of mast cells in affected tissues from patients with chronic rhinosinusitis (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 (CPA3), using real-time PCR, and assessed the presence of mast cell proteases using ELISA and immunohistochemistry. We also performed immunofluorescence to observe the pattern of colocalization of the mast cell proteases. RESULTS: Tryptase mRNA and protein were significantly increased in nasal polyps frompatientswithCRSwNPcomparedwith uncinate tissue from patients with CRS or healthy subjects. We made the striking observation that therewere abundantmast cells localizedwithinglands of nasalpolyps and that these mast cells expressed all three proteases. We also observed increased numbers of mast cells in epithelium but not elsewhere within the lamina propria in nasal polyps. The mast cells detected in epithelium in nasal polyps were characterized by expression of tryptase and CPA3 but not chymase. CONCLUSIONS: Herein we demonstrate increased mast cells in epithelium and glands of nasal polyp tissue, and show that nasal polyp mast cells have unique phenotypes that vary by tissue location. These diverse subsets of mast cells may contribute to the pathogenesis of CRSwNP.