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Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2580-5. doi: 10.1073/pnas.0707854105. Epub 2008 Feb 4.

Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms.

Author information

1
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of FcepsilonRI by multivalent antigens. These granules contain a variety of biologically active inflammatory mediators; however, it is not clear whether these granules are homogenous or whether there is heterogeneity within the secretory granule population in mast cells. By using genetically altered mice lacking specific vesicle-associated SNARE membrane fusion proteins, we found that VAMP-8-deficient mast cells exhibited defects in FcepsilonRI-regulated exocytosis, whereas synaptobrevin 2- or VAMP-3-deficient mast cells did not. Surprisingly, the defect in secretion in VAMP-8-deficient mice was limited to the subpopulation of mast cell secretory granules containing serotonin and cathepsin D, whereas regulated exocytosis of secretory granules containing histamine and TNF-alpha was normal. Confocal microscopy confirmed that serotonin and histamine were present in distinct intracellular granules and that most serotonin-containing granules were VAMP-8-positive. Thus, this study demonstrates that mast cells do indeed possess distinct subsets of secretory granules and that these subsets use different SNARE isoforms for exocytosis.

PMID:
18250339
PMCID:
PMC2268179
DOI:
10.1073/pnas.0707854105
[Indexed for MEDLINE]
Free PMC Article
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