Protease activated receptor-2 mediated mucus secretion in airway submucosal gland

Abstract

[한글]

[영문]Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor, and its activation leads to various biological responses. PAR2 is expressed in airway epithelia and smooth muscle and plays an important role in airway inflammation. In this study, we showed that the activation of PAR2 induces mucus secretion from the human airway gland. We also dissected the mechanism of PAR2-induced mucus secretion in the porcine airway gland. Human tracheal tissues were obtained following tracheotomies, and pig tracheal tissues were obtained following robot surgery training. The mucosa with underlying glands were dissected from the cartilage of the tracheal tissues, pinned mucosal side up at the gas/bath solution interface of a physiological chamber, and covered with oil so that secretions from individual glands could be visualized as spherical bubbles in the oil. Secretion rates were determined by optical monitoring of bubble diameter. The Ca2+-sensitive dye Fura2-AM was used to determine intracellular Ca2+ concentration ([Ca2+]i) by means of spectroflurometry in dissected airway gland. Stimulation of human tracheal mucosa with PAR2-activating peptide (AP) elevated intracellular Ca2+ and induced glandular secretion equal to about 20% of the carbachol response in the human airway. Porcine gland tissue was more sensitive to PAR2-AP, which is dependent on Ca2+ and anion secretion. Endogenous PAR2 activators, trypsin, and neutrophil elastase, also induced mucus secretion from airway gland. PAR2-induced mucus secretion was preserved in ΔF508 CFTR mutant mice.PAR2-AP is a strong agonist for mucus secretion from the airway gland that is Ca2+-dependent and CFTR-independent. Because PAR2 is involved in airway host defense mechanisms by stimulating airway mucus secretion from the submucosal gland, future research should investigate the potential of this receptor as a target for therapeutic intervention in the airway defense system.