Differential secretion of cytokines

Abstract

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.