期刊
COMMUNICATIONS BIOLOGY
卷 1, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s42003-018-0081-z
关键词
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资金
- Canadian Institutes of Health Research (CIHR) [MOP 89478]
- Mayo Foundation
- United States National Institutes of Health (NIH) [HL065228, RR0109709, HL058723]
- Natural Sciences and Engineering Research Council of Canada Postdoctoral Fellowship
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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