IL-1 induces vesicular secretion of IL-6 without degranulation from human mast cells.
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.
Department of Biochemistry, Tufts University School of Medicine, Boston, MA 02111, USA.
Kristiana
K
Kandere-Grzybowska
Richard
R
Letourneau
Duraisamy
D
Kempuraj
Jill
J
Donelan
Sarah
S
Poplawski
William
W
Boucher
Achilles
A
Athanassiou
Theoharis C
TC
Theoharides
D002118:Calcium / Q000502:physiology; D015550:Cell Degranulation / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D005312:Fetal Blood; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D007424:Intracellular Fluid / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D012697:Serine Endopeptidases / Q000378:metabolism / Q000648:ultrastructure; D053802:Tryptases
D007375:Interleukin-1; D015850:Interleukin-6; D012697:Serine Endopeptidases; D053802:Tryptases; D002118:Calcium