A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils

M. R. Logan, P. Lacy, S. O. Odemuyiwa, M. Steward, F. Davoine, H. Kita, R. Moqbel

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Background: Granulocyte exocytosis is proposed to be critically dependent on the interaction of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptors (SNAREs) located on granules/vesicles (v-SNAREs) and plasma membrane (t-SNAREs). Previous studies indicated that the v-SNARE, vesicle-associated membrane protein (VAMP)-2, as well as t-SNAREs (SNAP-23, syntaxin-4 and -6) are implicated in exocytosis from human granulocytes. Vesicle-associated membrane proteins-7 and -8 have been implicated in endosome/lysosome trafficking, however, their role in granulocyte exocytosis remains obscure. Objective: We sought to investigate the expression and functional role of SNARE isoforms in the secretion of different granule-derived mediators in human eosinophils and neutrophils. Methods: The expression of SNAREs was determined by subcellular fractionation and flow cytometry. SNARE-specific antibodies were examined for their ability to impair mediator release from permeabilized eosinophils and neutrophils. Results: Vesicle-associated membrane proteins-7 and -8 were localized to granule and membrane-enriched fractions in eosinophils and neutrophils, whereas syntaxin-6 was not detectable. In permeabilized cells, anti-VAMP-7, but not anti-VAMP-8, antibody impaired the secretion of all mediators examined (in eosinophils, eosinophil peroxidase and eosinophil-derived neurotoxin; in neutrophils, myeloperoxidase, lactoferrin and matrix metalloprotease-9) in a dose-dependent manner. In contrast, anti-VAMP-2 modestly and selectively impaired secretion from small granules and vesicles. Syntaxin-4, but not syntaxin-6, was found to interact with SNAP-23 and was partially involved in mediator secretion from multiple compartments. Conclusion: Our observations indicate for the first time a critical role for VAMP-7 in both eosinophil and neutrophil mediator release.

Original languageEnglish (US)
Pages (from-to)777-784
Number of pages8
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume61
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • Exocytosis
  • Granulocytes
  • Soluble N-ethylmaleimide-sensitive factor attachment protein receptors
  • Vesicle-associated membrane protein-7

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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