IL-1 Induces Vesicular Secretion of IL-6 without Degranulation from Human Mast Cells

• Published in: The Journal of immunology (1950) 2003-11, Vol.171 (9), p.4830-4836
• Main Authors: Kandere-Grzybowska, Kristiana, Letourneau, Richard, Kempuraj, Duraisamy, Donelan, Jill, Poplawski, Sarah, Boucher, William, Athanassiou, Achilles, Theoharides, Theoharis C
• Format: Article
• Language: English
• Subjects: Calcium - physiology; Cell Degranulation - physiology; Cell Line, Tumor; Cells, Cultured; Cytoplasmic Vesicles - enzymology; Cytoplasmic Vesicles - metabolism; Cytoplasmic Vesicles - physiology; Cytoplasmic Vesicles - ultrastructure; Fetal Blood; Humans; Interleukin-1 - physiology; Interleukin-6 - biosynthesis; Interleukin-6 - metabolism; Intracellular Fluid - chemistry; Intracellular Fluid - enzymology; Intracellular Fluid - metabolism; Intracellular Fluid - physiology; Mast Cells - enzymology; Mast Cells - metabolism; Mast Cells - physiology; Mast Cells - ultrastructure; Microscopy, Immunoelectron; Serine Endopeptidases - metabolism; Serine Endopeptidases - ultrastructure; Tryptases
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.9.4830

Fc epsilon RI cross-linkage in mast cells results in release of granule-associated mediators, such as histamine and proteases, as well as the production of numerous cytokines, including IL-6. Mast cells have been increasingly implicated in inflammatory processes where explosive degranulation is not commonly observed. Here, we show that IL-1 stimulates secretion of IL-6 without release of the granule-associated protease tryptase in normal human umbilical cord blood-derived mast cells (hCBMCs). IL-6 secretion stimulated by IL-1 in hCBMCs is potentiated by priming with IL-4 and reflects the higher levels of IL-6 secreted from human leukemic mast cell line (HMC-1). Stimulating HMC-1 cells by both IL-1 and TNF-alpha results in synergistic secretion of IL-6. IL-6 is de novo synthesized, as its secretion is blocked by inhibitors of transcription or protein synthesis. IL-1 does not increase intracellular calcium 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 contribute to the development of inflammation, where the importance of IL-6 has been recognized.