Protease-activated receptor 2-dependent fluid secretion from airway submucosal glands by house dust mite extract

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• 作者：Hyung-Ju Cho ; MD ; PhD^a ; ^&lowast ; ; ^&Dagger ; ; Hyun Jae Lee ; MSc^b ; ^c ; ^e ; ^&Dagger ; ; Sang Cheol Kim ; MD^b ; Kyubo Kim ; MD^a ; Yoo Suk Kim ; MD^b ; Chang-Hoon Kim ; MD ; PhD^b ; ^c ; ^d ; Jeung-Gweon Lee ; MD ; PhD^b ; Joo-Heon Yoon ; MD ; PhD^b ; ^c ; ^d ; ^e ; ^{jhyoon@yuhs.ac} ; Jae Young Choi ; MD ; PhD^b ; ^e ; ^{jychoi@yuhs.ac}
• 关键词：House dust mites ; submucosal gland ; allergy ; chronic rhinosinusitis ; protease-activated receptor ; nasal
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 出版时间：February, 2012
• 年：2012
• 卷：129
• 期：2
• 页码：529-535.e5
• 全文大小：1104 K

文摘

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Background

The submucosal gland (SMG) is important in the control of airway surface fluid. Protease-activated receptor (PAR) 2 contributes to the pathophysiology of allergies in response to nonspecific allergens bearing proteases and anion secretion. House dust mites (HDMs) have abundant proteases that can activate PAR2, but little is known about the direct effect of HDM on SMG secretion.

Objective

The aim of this study was to investigate the effect of HDMs on glandular secretion and its mechanism in allergic patients, patients with chronic rhinosinusitis (CRS), or both.

Methods

Inferior nasal turbinates were harvested from 55 patients and classified into 4 groups (the control, allergic rhinitis [AR], CRS, and AR+CRS groups). A?microscope attached to a digital camera was used to quantify mucus bubbles from individual SMGs while stimulated with HDM extract, PAR2-activating peptide, and carbachol. PAR2 expression in the SMG?was determined by means of immunostaining with anti-PAR2 mAb.

Results

HDM induced a significantly higher secretion rate and number of responding glands in the AR and AR+CRS groups than in the control group. Interestingly, patients in the CRS group, who had no HDM-specific IgE antibody, showed a higher response than the control group, and its response was suppressed by a PAR2-selective antagonist. The responses to PAR2-activating peptide were similar to those to HDM, and their secretion rates positively correlated with HDM responses. PAR2 was highly expressed in all 3 disease groups with immunostaining.

Conclusions

HDM allergens can induce glandular secretion in patients with AR, CRS, or both, and PAR2 represents a possible mechanism for nonspecific hyperreactivity in inflammatory airway diseases.