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Human mast cell degranulation is distinguished from selective secretion of TNF through intracellular calcium, energy and mitochondrial morphology dynamics
Author(s) -
Zhang Bodi,
Angelidou Asimenia,
Alysandratos KonstantinosDionysios,
Tagen Michael,
Kempuraj Duraisamy,
Asadi Shahrzad,
Theoharides Theoharis
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.966.3
Subject(s) - degranulation , secretion , calcium in biology , mast cell , calcium , microbiology and biotechnology , intracellular , mitochondrion , oligomycin , stimulation , lipopolysaccharide , chemistry , biology , endocrinology , biochemistry , immunology , receptor , enzyme , atpase , organic chemistry
The mast cells are unique bone‐marrow derived immune cells that can secrete pre‐stored mediators through degranulation, such as triggered by Substance P (SP) or release de novo synthesized cytokines stimulated by lipopolysaccharide (LPS). However, differences in these modes secretion are largely unknown. We examined energy production, calcium homeostasis and mitochondrial morphological dynamics in LAD2 mast cell degranulation and selective secretion. A) Mast cells degranulation triggered by SP (10 μM) had two times higher energy consumption than LPS (10 ng/ml) treated cells and control cells. Mitochondria ATP pump blocker Oligomycin (2 μM) inhibited 68% of TNF secretion due to degranulation, but has little effects on de novo synthesized TNF release. B) Mast cells have increased intracellular calcium level 10 seconds after SP stimulation, while LPS did not induce significant intracellular calcium increase. C) Mitochondrial uncoupling protein 2 (UCP2) absorbs calcium from intracellular region and protects cells from calcium toxicity. UCP2 mRNA expression level enhanced ten times after 7 hours SP stimulation, but was unchanged with LPS. D) Mitochondria morphology has tight connection with its function. We showed mast cells treated with SP (10 μM) had significant mitochondrial fragmentation, which was no appeared in LPS stimulation. The present findings indicate that secretion from human mast cells can occur through distinct pathways. Mitochondria may play key role in regulating mast cell activation. This work was supported in part by NIH grant R01 AR47652 to TCT.