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

Lian Willetts; Lindsey C. Felix; Elizabeth A. 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

doi:10.1038/s42003-018-0081-z

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

Lian Willetts, Lindsey C. Felix, Elizabeth A. 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-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.

Original language	English (US)
Article number	83
Journal	Communications Biology
Volume	1
Issue number	1
DOIs	https://doi.org/10.1038/s42003-018-0081-z
State	Published - Dec 1 2018

ASJC Scopus subject areas

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

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Willetts, L., Felix, L. C., Jacobsen, E. A., Puttagunta, L., Condjella, R. M., Zellner, K. R., Ochkur, S. I., Kim, J. D., Luo, H., Lee, N. A., Lee, J. J., Moqbel, R., & Lacy, P. (2018). Vesicle-associated membrane protein 7-mediated eosinophil degranulation promotes allergic airway inflammation in mice. Communications Biology, 1(1), Article 83. https://doi.org/10.1038/s42003-018-0081-z

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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",

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doi = "10.1038/s42003-018-0081-z",

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AU - Puttagunta, Lakshmi

AU - Condjella, Rachel M.

AU - Zellner, Katie R.

AU - Ochkur, Sergei I.

AU - Kim, John D.

AU - Luo, Huijun

AU - Lee, Nancy A.

AU - Lee, James J.

AU - Moqbel, Redwan

AU - Lacy, Paige

PY - 2018/12/1

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N2 - 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.

AB - 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.

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

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