IL-1 Induces vesicular secretion of IL-6 without degranulation from human mast cells
Kristiana Kandere-Grzybowska, Richard Letourneau, Duraisamy Kempuraj, Jill Donelan,Sarah Poplawski, William Boucher, Achilles Athanassiou, and Theoharis C. Theoharides
J Immunol 2003; 171:4830-4836
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FcRI cross-linkage in mast cells results in release of granule-associated mediators, such as histamine and proteases, as well as theproduction of numerous cytokines, including IL-6. Mast cells have been increasingly implicated in inflammatory processes whereexplosive degranulation is not commonly observed. Here, we show that IL-1 stimulates secretion of IL-6 without release of thegranule-associated protease tryptase in normal human umbilical cord blood-derived mast cells (hCBMCs). IL-6 secretion stimulatedby IL-1 in hCBMCs is potentiated by priming with IL-4 and reflects the higher levels of IL-6 secreted from human leukemicmast cell line (HMC-1). Stimulating HMC-1 cells by both IL-1 and TNF-results in synergistic secretion of IL-6. IL-6 is de novosynthesized, as its secretion is blocked by inhibitors of transcription or protein synthesis. IL-1 does not increase intracellularcalcium ion levels in either hCBMCs or HMC-1 cells, and IL-6 stimulation proceeds in the absence of extracellular calcium ions.Ultrastructural Immunogold localization shows that IL-6 is excluded from the secretory granules and is compartmentalized in 40-to 80-nm vesicular structures. Selective secretion of IL-6 from mast cells appears distinct from degranulation and may contributeto the development of inflammation, where the importance of IL-6 has been recognized. The Journal of Immunology, 2003, 171:4830–4836.’, ‘
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