Rhinitis, sinusitis, and upper airway disease
Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps

https://doi.org/10.1016/j.jaci.2012.02.046Get rights and content

Background

Although chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is characterized by TH2 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.

Section snippets

Patients

Patients with CRS were recruited from the allergy and otolaryngology clinics at Northwestern University and the Northwestern Sinus Center. Sinonasal and polyp tissues were obtained from routine functional endoscopic sinus surgery in patients with CRS. All subjects met the criteria for CRS as defined by the Sinus and Allergy Health Partnership.1

Patients with an isolated antrochoanal polyp, cystic fibrosis, or unilateral NPs were excluded from the study. Details of subjects' characteristics are

Mast cell expression and distribution in patients with CRS

Sinonasal and polyp tissues were collected from 70 subjects with CRSsNP, 91 subjects with CRSwNP, and 42 control subjects to determine the levels of expression of mast cells and their products in patients with CRS. Subject characteristics are shown in Table I.

To estimate the levels of mast cells in nasal mucosa, we first assessed the expression of mRNA for tryptase in UT from patients with CRSsNP, patients with CRSwNP, and controls, as well as in NPs from patients with CRSwNP. The expression of

Discussion

The current study provides the first in-depth description of the expression, distribution, and phenotype of mast cells in NPs from patients with CRSwNP. We found increased levels of mast cells in NPs than in UT from control subjects and patients with CRS (Fig 1). We made the striking observation that mast cells were present within glandular tissues contained in NPs but were almost never detected within glands in UT from either patients or controls. Another important original finding was that

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    This study was supported by National Institutes of Health grants R37HL068546-27, R01HL078860, and RO1AI072570 and the Ernest S. Bazley Trust.

    Disclosure of potential conflict of interest: R.C. Kern and R.P. Schleimer received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.

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