Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract Hyung-Ju Cho, MD, PhD, Hyun Jae Lee,

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Presentation transcript:

Protease-activated receptor 2–dependent fluid secretion from airway submucosal glands by house dust mite extract Hyung-Ju Cho, MD, PhD, Hyun Jae Lee, MSc, Sang Cheol Kim, MD, Kyubo Kim, MD, Yoo Suk Kim, MD, Chang-Hoon Kim, MD, PhD, Jeung-Gweon Lee, MD, PhD, Joo-Heon Yoon, MD, PhD, Jae Young Choi, MD, PhD Journal of Allergy and Clinical Immunology Volume 129, Issue 2, Pages 529-535.e5 (February 2012) DOI: 10.1016/j.jaci.2011.11.024 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Quantitative measurement of glandular secretion. A, Schematic drawing showing harvest of nasal mucosa (inset) from the inferior nasal turbinate. B, Experimental setup. C, Mucus bubbles from glands under oil are visualized by using bright-field microscopy and side-light illumination. D, Example of mucus bubbles formed on the surface of nasal turbinates 30 minutes after stimulation with 10 μmol/L carbachol. Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Responses to HDM. A, Plots of averaged secretion rates versus time for each group. ∗P < .05, Kruskal-Wallis test. B, Representative images of glandular secretion from patient 26 before (B1) and 20 minutes after (B2) HDM treatment. Arrows indicate bubbles. C, Comparison of HDM-induced secretion rates. D, Comparison of HDM-responsive glands (as a percentage). ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 compared with the control group. Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 PAR2 expression in SMGs. A, Example of immunostaining in a control patient (no. 6) and a patient with CRS (no. 24). B, Comparison of the degree of PAR2 expression in the control, AR, CRS, and AR+CRS groups. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001 compared with the control group. Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Response to PAR2-AP or carbachol and inhibition by PAR2 antagonist. A, Comparison of PAR2-AP–induced secretion rates. B, Comparison of PAR2-AP–responsive glands. C, Comparison of carbachol (CARB)–induced secretion rates. D, Inhibitory effect of ENMD-1068 (PAR2-selective antagonist) on HDM-induced response. ∗P < .05 and ∗∗P < .01 compared with the control group. Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Dose-dependent HDM (10 or 100 μg/mL)–induced responses. ∗P < .05, ∗∗P < .01, and ∗∗∗P < 0.0001, Mann-Whitney test. Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 The HDM- or PAR2-AP–induced responses did not correlate with the carbachol-induced responses but instead correlated with the PAR2-AP–induced responses. A, Correlation between HDM- and carbachol-induced responses (Rs = −0.0247, P = .7029). B, Correlation between PAR2-AP– and carbachol-induced responses (Rs = 0.1072, P = .1388). C, Correlation between HDM- and PAR2-AP–induced responses in all 4 groups (Rs = 0.7162, P < .0001). D, Secretion rate according to tissue age. Correlations were not shown at less than 36 hours between postharvest time and secretion rates when treated with HDM, PAR2-AP, and carbachol (HDM: Rs = −0.059, P = .738; PAR2-AP: Rs = −0.040, P = .854; carbachol: Rs = −0.291, P = .090). Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Correlation between HDM- and PAR2-AP–induced responses (control group: Rs = 0.6527; AR group: Rs = 0.7056; CRS group: Rs = 0.6697; and AR+CRS group: Rs = 0.6099; P < .0001 in all groups). Journal of Allergy and Clinical Immunology 2012 129, 529-535.e5DOI: (10.1016/j.jaci.2011.11.024) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions