Τίτλος:
Mitochondria distinguish granule-stored from de novo synthesized tumor necrosis factor secretion in human mast cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background: 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. Methods: 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. Results: 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 compared to de novo synthesized TNF release induced by lipopolysaccharide. This mitochondrial translocation is confirmed using primary human umbilical cord blood-derived mast cells stimulated by an allergic trigger (IgE/streptavidin). Conclusion: Our findings indicate that unique mitochondrial functions distinguish granule-stored from newly synthesized TNF release from human mast cells, thus permitting the versatile involvement of mast cells in different biological processes. Copyright © 2012 S. Karger AG, Basel.
Συγγραφείς:
Zhang, B.
Weng, Z.
Sismanopoulos, N.
Asadi, S.
Therianou, A.
Alysandratos, K.-D.
Angelidou, A.
Shirihai, O.
Theoharides, T.C.
Περιοδικό:
International Archives of Allergy and Immunology
Λέξεις-κλειδιά:
calcium; immunoglobulin E; lipopolysaccharide; oligomycin; oxygen; streptavidin; substance P; tumor necrosis factor, allergy; article; calcium cell level; cell energy; cell function; cell granule; cell stimulation; cell surface; cellular distribution; confocal microscopy; controlled study; cytokine production; cytokine release; energy consumption; enzyme linked immunosorbent assay; gene expression; gene translocation; human; human cell; leukemia cell; mast cell; mitochondrion; molecular dynamics; oxygen consumption; priority journal; protein localization; real time polymerase chain reaction; reverse transcription polymerase chain reaction; signal transduction; umbilical cord blood, Calcium; Cell Degranulation; Cell Line, Tumor; Cells, Cultured; Humans; Lipopolysaccharides; Mast Cells; Mitochondria; Oligomycins; RNA, Messenger; Secretory Vesicles; Substance P; Tumor Necrosis Factor-alpha; Uncoupling Agents
