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, Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, T6G 2S2 Alberta Canada. Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, 85259 AZ USA. Department of Immunology, University of Manitoba, Winnipeg, R3T 2N2 Manitoba Canada.
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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