Commun Biol. 2018 Jun 29;1:83. doi: 10.1038/s42003-018-0081-z. eCollection 2018.
Willetts, L; Felix, LC; Jacobsen, EA; Puttagunta, L; Condjella, RM; Zellner, KR; Ochkur, SI; Kim, JD; Luo, H; Lee, NA; Lee, JJ; Moqbel, R; Lacy, P
Alberta Respiratory Centre (ARC) Research, Department of Medicine and Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, T6G 2S2 Alberta Canada. Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology
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-7 f/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.
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