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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms
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Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms

机译：肥大细胞具有不同的分泌性颗粒亚群，其胞吐作用受不同的SNARE亚型调节

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摘要

Mast cells degranulate and release the contents of intracellular secretory granules in response to the cross-linking of FcεRI 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 FcεRI-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-α was normal. Confocal microscopy confirmed that serotonin and histamine were present in distinct intracellular granules and that most serotonin-containing granules were VAMP-8-posi-tive. 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.
机译：肥大细胞脱粒并释放细胞内分泌颗粒的内容物，以响应FcεRI通过多价抗原的交联。这些颗粒含有多种具有生物活性的炎症介质。然而，尚不清楚这些颗粒是否同质或肥大细胞的分泌颗粒群内是否存在异质性。通过使用缺少特定的囊泡相关的SNARE膜融合蛋白的基因改造小鼠，我们发现VAMP-8缺陷的肥大细胞在FcεRI调控的胞吐作用中表现出缺陷，而突触素2或VAMP-3缺陷的肥大细胞则没有。出乎意料的是，VAMP-8缺陷型小鼠的分泌缺陷仅限于含有5-羟色胺和组织蛋白酶D的肥大细胞分泌颗粒亚群，而含有组胺和TNF-α的分泌颗粒的调控胞吐作用是正常的。共聚焦显微镜证实5-羟色胺和组胺存在于不同的细胞内颗粒中，并且大多数含有5-羟色胺的颗粒是VAMP-8阳性的。因此，这项研究表明肥大细胞确实确实拥有分泌颗粒的不同子集，并且这些子集使用不同的SNARE亚型进行胞吐作用。

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