Differential secretion of cytokines.
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.
Moqbel
Redwan
R
Pulmonary Research Group, University of Alberta, Edmonton, Alberta, Canada. Redwan.moqbel@ualberta.ca
Coughlin
Jason J
JJ
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000737:chemistry / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology; D021381:Protein Transport; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology; D050600:SNARE Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D060245:Tetraspanin 29
D000906:Antibodies; D015703:Antigens, CD; C515456:CCL11 protein, human; C554869:CD9 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D018925:Chemokines; D019742:Chemokines, CC; D016207:Cytokines; D007378:Interleukins; C105298:LILRA2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D050600:SNARE Proteins; D060245:Tetraspanin 29; D007371:Interferon-gamma; D047209:Eosinophil Peroxidase