Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells.

International Archives of Allergy and Immunology
Bodi ZhangTheoharis C Theoharides

Abstract

Mast cells are immune cells derived from hematopoietic precursors that mature in the tissue microenvironment. Mast cells are critical for allergic, immune and inflammatory processes, many of which involve tumor necrosis factor (TNF). These cells uniquely store TNF in their secretory granules. Upon stimulation, mast cells rapidly (30 min) secrete β-hexosaminidase and granule-stored TNF through degranulation, but also increase TNF mRNA and release de novo synthesized TNF 24 h later. The regulation of these two distinct pathways is poorly understood. Human LAD2 leukemic mast cells are stimulated by substance P. TNF secretion and gene expression were measured by ELISA and real-time PCR, and mitochondrial dynamics was observed in live cells under confocal microscopy. Cell energy consumption was measured in terms of oxygen consumption rate. Here, we show that granule-stored TNF is preformed, and its secretion from LAD2 mast cells stimulated by substance P (1) exhibits higher energy consumption and is inhibited by the mitochondrial ATP pump blocker oligomycin, (2) shows rapid increase in intracellular calcium levels, and (3) exhibits reversible mitochondrial translocation, from a perinuclear distribution to the cell surface, as compar...Continue Reading

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Citations

Jul 4, 2012·BMC Pediatrics·Asimenia AngelidouTheoharis C Theoharides
Apr 11, 2013·Journal of Neuroinflammation·Theoharis C TheoharidesArti B Patel
Mar 4, 2014·The Journal of Allergy and Clinical Immunology·Tal Hadad ErlichEhud Razin
Jul 26, 2015·Fish & Shellfish Immunology·Anying ZhangHong Zhou
May 6, 2015·European Journal of Pharmacology·Theoharis C TheoharidesIsaac Melamed
Dec 17, 2014·The Journal of Allergy and Clinical Immunology·Zuyi WengTheoharis C Theoharides
Feb 12, 2015·Journal of Neuroimmunology·Theoharis C TheoharidesRobert Doyle
Mar 24, 2017·Nature Reviews. Rheumatology·Timo GaberFrank Buttgereit
May 3, 2014·Expert Review of Clinical Immunology·Anastasia I PetraTheoharis C Theoharides
Mar 5, 2016·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Dang Van CuongJin Han
Dec 4, 2019·Endocrine, Metabolic & Immune Disorders Drug Targets·Thea MagroneEmilio Jirillo
Mar 19, 2019·Expert Review of Clinical Immunology·Theoharis C TheoharidesHuali Ren
May 4, 2017·Proceedings of the National Academy of Sciences of the United States of America·Alexandra TaracanovaTheoharis C Theoharides
May 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Arnau Navinés-FerrerMargarita Martin
Jun 29, 2021·Frontiers in Cellular Neuroscience·Lijia MaiWenguo Fan
Aug 10, 2021·Frontiers in Cell and Developmental Biology·Xin LiuJunli Guo

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