A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils.
Allergy
; 61(6): 777-84, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16677249
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Eosinófilos
/
Proteínas R-SNARE
/
Exocitose
/
Neutrófilos
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Allergy
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos