Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice

Lian Willetts, Lindsey C. Felix, Elizabeth Jacobsen, Lakshmi Puttagunta, Rachel M. Condjella, Katie R. Zellner, Sergei I. Ochkur, John D. Kim, Huijun Luo, Nancy A Lee, James J. Lee, Redwan Moqbel, Paige Lacy

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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.

Original languageEnglish (US)
Article number83
JournalCommunications Biology
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2018

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R-SNARE Proteins
eosinophils
Eosinophils
membrane proteins
inflammation
Inflammation
mice
Allergies
SNARE Proteins
Methacholine Chloride
Interleukin-5
Ovalbumin
Pathology
Allergens
Machinery
Fusion reactions
Genes
interleukin-5
Adoptive Transfer
ovalbumin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Medicine (miscellaneous)

Cite this

Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice. / Willetts, Lian; Felix, Lindsey C.; Jacobsen, Elizabeth; Puttagunta, Lakshmi; Condjella, Rachel M.; Zellner, Katie R.; Ochkur, Sergei I.; Kim, John D.; Luo, Huijun; Lee, Nancy A; Lee, James J.; Moqbel, Redwan; Lacy, Paige.

In: Communications Biology, Vol. 1, No. 1, 83, 01.12.2018.

Research output: Contribution to journalArticle

Willetts, L, Felix, LC, Jacobsen, E, Puttagunta, L, Condjella, RM, Zellner, KR, Ochkur, SI, Kim, JD, Luo, H, Lee, NA, Lee, JJ, Moqbel, R & Lacy, P 2018, 'Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice', Communications Biology, vol. 1, no. 1, 83. https://doi.org/10.1038/s42003-018-0081-z
Willetts, Lian ; Felix, Lindsey C. ; Jacobsen, Elizabeth ; Puttagunta, Lakshmi ; Condjella, Rachel M. ; Zellner, Katie R. ; Ochkur, Sergei I. ; Kim, John D. ; Luo, Huijun ; Lee, Nancy A ; Lee, James J. ; Moqbel, Redwan ; Lacy, Paige. / Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice. In: Communications Biology. 2018 ; Vol. 1, No. 1.
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