Regulated and constitutive exocytosis of cytokines. Representative pathways are shown for SNARE-mediated regulated (eosinophil, left) and constitutive (macrophage, right) release of CCL5/RANTES and TNF, respectively. In regulated exocytosis, IFNγ-stimulated eosinophils release preformed CCL5/RANTES by piecemeal degranulation from their crystalloid granules via small secretory vesicles that express the Q-SNARE VAMP-2 (red) for binding to cognate R-SNAREs, SNAP-23 (green), and syntaxin-4 (blue). Constitutive exocytosis occurs during stimulation by LPS, which leads to continuous trafficking of newly synthesized pro-TNF from the ER through the Golgi to recycling endosomes, which use the SNARE complex Vti1b/syntaxin-6/syntaxin-7 to transport pro-TNF to recycling endosomes. From the recycling endosome to the cell membrane, the R-SNARE VAMP-3 (red) on recycling endosomes binds to Q-SNAREs SNAP-23 (green) and syntaxin-4 (blue) in the cell membrane to fuse the recycling endosomes for TNF cleavage and release at the cell exterior. Rab11a (purple) is involved in directing SNARE binding at the cell membrane.