Moqbel Redwan, Coughlin Jason J
Pulmonary Research Group, University of Alberta, Edmonton, Alberta, Canada.
Sci STKE. 2006 Jun 6;2006(338):pe26. doi: 10.1126/stke.3382006pe26.
Eosinophil granules store a vast array of cytokines and chemokines, many of which possess opposing activities. Specific stimuli can induce the release of entire granules or selective mediators through a process termed piecemeal degranulation. Until recently, the mechanisms that governed the decision to opt for either of these processes were unknown. Recent research has identified a mechanism through which differential secretion occurs during piecemeal degranulation. Eotaxin stimulation of eosinophils induces the selective mobilization of the granule-stored alpha chain of the interleukin-4 (IL-4) receptor into secretory vesicles. This process selectively recruits IL-4 to these vesicles and facilitates its differential secretion. There is also recent evidence for a mechanism of differential mobilization and membrane fusion of secretory vesicles versus granules. These two compartments possess a different set of SNARE and Rab molecules as vesicle fusion and transport-docking proteins, respectively. This presumably allows differential regulation of the processes of mobilization and plasma membrane fusion. These findings provide a model to explain the mechanism by which eosinophils, and likely many other cell types, differentially secrete cytokines and chemokines.
嗜酸性粒细胞颗粒储存着大量的细胞因子和趋化因子，其中许多具有相反的活性。特定刺激可通过一种称为颗粒逐片释放的过程诱导整个颗粒或选择性介质的释放。直到最近，决定选择这两种过程之一的机制仍不清楚。最近的研究发现了一种机制，通过该机制在颗粒逐片释放过程中发生差异分泌。嗜酸性粒细胞趋化因子对嗜酸性粒细胞的刺激诱导颗粒储存的白细胞介素-4（IL-4）受体α链选择性动员到分泌小泡中。这一过程选择性地将IL-4募集到这些小泡中，并促进其差异分泌。最近也有证据表明存在分泌小泡与颗粒的差异动员和膜融合机制。这两个区室分别具有一组不同的SNARE和Rab分子，作为囊泡融合和转运对接蛋白。这大概允许对动员和质膜融合过程进行差异调节。这些发现提供了一个模型来解释嗜酸性粒细胞以及可能许多其他细胞类型差异分泌细胞因子和趋化因子的机制。
