Mast cell–derived plasminogen activator inhibitor type 1 promotes airway inflammation and remodeling in a murine model of asthma Ara Jo, PhD, Sun H.

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Presentation transcript:

Mast cell–derived plasminogen activator inhibitor type 1 promotes airway inflammation and remodeling in a murine model of asthma Ara Jo, PhD, Sun H. Lee, PhD, Dong-Young Kim, MD, PhD, Seung-Jae Hong, MD, PhD, Michael N. Teng, PhD, Narasaiah Kolliputi, PhD, Richard F. Lockey, MD, Robert P. Schleimer, PhD, Seong H. Cho, MD Journal of Allergy and Clinical Immunology Volume 142, Issue 1, Pages 294-297.e5 (July 2018) DOI: 10.1016/j.jaci.2018.01.040 Copyright © 2018 Terms and Conditions

Fig 1 Inflammation in lung tissues of PBS- or OVA-challenged mice. A, Number of total inflammatory cells and eosinophils per HPF in BALF from PBS- or OVA-challenged mice. Data are expressed as means ± SEs. *P < .05 PBS versus OVA. #P < .05 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. ##P < .01 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. B, Representative hematoxylin and eosin staining for histopathologic changes in lung sections of PBS- or OVA-challenged mice. WT, WT mice; MC KO, Kitw-sh/w-sh mice; WT MC KI, WT BMCMC→Kitw-sh/w-sh mice; and PAI-1−/− MC KI, PAI-1−/− BMCMC→Kitw-sh/w-sh mice. KI, Knock-in; KO, knockout. Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions

Fig 2 Airway remodeling in lung tissues of PBS- or OVA-challenged mice. A, Lung sections were stained with periodic acid–Schiff to assess goblet cell hyperplasia. Original magnification ×400. The number of periodic acid–Schiff–positive cells per 100 μm of basement membrane is visualized graphically with ImageJ software (right panel). *P < .05 PBS versus OVA. #P < .05 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. ##P < .01 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. B, Masson trichrome staining was conducted to evaluate collagen deposition (blue). Original magnification ×200. *P < .05 PBS versus OVA. #P < .05 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. ##P < .01 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. C, AHR to increasing concentrations of methacholine (0-333 mg/mL) was measured by using the Buxco apparatus and was reported as percentage change of Penh per baseline value. #P < .05 OVA-challenged WT MC KI versus OVA-challenged PAI-1−/− MC KI. All data are expressed as means ± SEs. WT, WT mice; MC KO, Kitw-sh/w-sh mice; WT MC KI, WT BMCMC→Kitw-sh/w-sh mice; and PAI-1−/− MC KI, PAI-1−/− BMCMC→Kitw-sh/w-sh mice. Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions

Fig E1 A, Histamine release from BMCMCs derived from WT and PAI-1−/− mice. A, BMCMCs derived from WT and PAI-1−/− mice were stimulated by using IgE receptor cross-linking, and histamine levels were measured in supernatants from the cells by using ELISA (n = 3). B, PAI-1 levels were measured in cell supernatants by means of ELISA (n = 3). DNP, 2,4-dinitrophenol. Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions

Fig E2 Numbers of tissue MCs in lungs of MC knock-in mice reconstituted with WT or PAI-1–deficient MCs. Tissue MCs were stained with toluidine blue, and numbers were measured in lung tissue sections from MC knock-in mice reconstituted with WT or PAI-1–deficient MCs. C, WT BMCMC→Kitw-sh/w-sh mice; D, PAI-1−/− BMCMC→Kitw-sh/w-sh mice. There was no significant (NS) difference between groups C and D (PBS or OVA challenge). Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions

Fig E3 Immunohistochemistry of PAI-1 and toluidine blue staining for MCs in lung tissue. A, Data show a representative image of PAI-1 (brown, black arrow) and toluidine blue (purple, purple arrow) staining. Black arrowhead indicates normal positive PAI-1 staining of the blood vessel. Original magnification ×400. MC KO, Kitw-sh/w-sh mice; PAI1−/− MC KI, PAI-1−/− BMCMC→Kitw-sh/w-sh mice; WT, WT mice; WT MC KI, WT BMCMC→Kitw-sh/w-sh mice. B, Cellular sources of PAI-1: mast cell, macrophage, and epithelial cells. Original magnification ×600. Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions

Fig E4 TSLP production from normal bronchial epithelial cells. Normal human bronchial epithelial cells (NHBE) were stimulated by IL-4/double-stranded RNA (polyinosinic:polycytidylic acid [poly I:C]) with or without PAI-1 for 6 hours, and levels of TSLP mRNA (A) and protein (B) from NHBE cells were measured by using RT-PCR (cells) and ELISA (culture supernatants), respectively (triplicate with 2 independent experiments). Journal of Allergy and Clinical Immunology 2018 142, 294-297.e5DOI: (10.1016/j.jaci.2018.01.040) Copyright © 2018 Terms and Conditions