@article{99aeb59a7562440296a39f156e671af4,
title = "Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice",
abstract = "Eosinophil degranulation is a determining factor in allergy-mediated airway pathology. Receptor-mediated degranulation in eosinophils requires vesicle-associated membrane protein 7 (VAMP-7), a principal component of the SNARE fusion machinery. The specific contribution of eosinophil degranulation to allergen-induced airway responses remains poorly understood. We generated mice with VAMP-7 gene deficiency exclusively in eosinophils (eoCRE/V7) from a cross using eosinophil-specific Cre recombinase-expressing mice crossed with VAMP-7f/f mice. Eosinophils from eoCRE/V7 mice showed deficient degranulation responses in vitro, and responses continued to be decreased following ex vivo intratracheal adoptive transfer of eoCRE/V7 eosinophils into IL-5/hE2/EPX−/− mice. Consistent with diminished degranulation responses, reduced airway hyperresponsiveness was observed in ovalbumin-sensitized and challenged eoCRE/V7 mice following methacholine inhalation. Therefore, VAMP-7 mediates eosinophil degranulation both in vitro and ex vivo, and this event augments airway hyperresponsiveness.",
author = "Lian Willetts and Felix, {Lindsey C.} and Jacobsen, {Elizabeth A.} and Lakshmi Puttagunta and Condjella, {Rachel M.} and Zellner, {Katie R.} and Ochkur, {Sergei I.} and Kim, {John D.} and Huijun Luo and Lee, {Nancy A.} and Lee, {James J.} and Redwan Moqbel and Paige Lacy",
note = "Funding Information: We acknowledge the technical assistance provided by the Mayo Clinic Rochester Electron Microscopy and Histology Core Facilities, and thank William E. LeSuer, Cheryl A. Protheroe, and Ralph S. Pero (Mayo Clinic), and Renjith Pillai (University of Alberta) for their support toward this study. We thank J{\"o}rg Fritz, McGill University, for critical review and editing of the manuscript. We also thank Tom Turner, Laboratory Medicine and Pathology, University of Alberta, for collecting histological data for this study. Finally, we thank Jessica Woulfe for artwork provided in Fig. 4a. The performance of these studies, including data analysis and manuscript preparation, was supported by resources from the Canadian Institutes of Health Research (CIHR; to R.M. and P.L. [MOP 89478]), the Mayo Foundation and grants from the United States National Institutes of Health (NIH; to J.J.L. [HL065228, RR0109709], to N.A.L. [[HL058723]). L.C.F. was supported by a Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s42003-018-0081-z",
language = "English (US)",
volume = "1",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}