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

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