The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Stimulated Human Mast Cells Secrete Mitochondrial Components That Have Autocrine and Paracrine Inflammatory Actions
Open accessAbstract
Mast cells are hematopoietically-derived tissue immune cells that participate in acquired and innate immunity, as well as in inflammation through release of many chemokines and cytokines, especially in response to the pro-inflammatory peptide substance P (SP). Inflammation is critical in the pathogenesis of many diseases, but the trigger(s) is often unknown. We investigated if mast cell stimulation leads to secretion of mitochondrial components and whether these could elicit autocrine and/or paracrine inflammatory effects. Here we show that human LAD2 mast cells stimulated by IgE/anti-IgE or by the SP led to secretion of mitochondrial particles, mitochondrial (mt) mtDNA and ATP without cell death. Mitochondria purified from LAD2 cells and, when mitochondria added to mast cells trigger degranulation and release of histamine, PGD(2), IL-8, TNF, and IL-1β. This stimulatory effect is partially inhibited by an ATP receptor antagonist and by DNAse. These results suggest that the mitochondrial protein fraction may also contribute. Purified mitochondria also stimulate IL-8 and vascular endothelial growth factor (VEGF) release from cultured human keratinocytes, and VEGF release from primary human microvascular endothelial cells. In order to investigate if mitochondrial components could be secreted in vivo, we injected rats intraperiotoneally (ip) with compound 48/80, which mimicks the action of SP. Peritoneal mast cells degranulated and mitochondrial particles were documented by transimission electron microscopy outside the cells. We also wished to investigate if mitochondrial components secreted locally could reach the systemic circulation. Administration ip of mtDNA isolated from LAD2 cells in rats was detected in their serum within 4 hr, indicating that extravascular mtDNA could enter the systemic circulation. Secretion of mitochondrial components from stimulated live mast cells may act as "autopathogens" contributing to the pathogenesis of inflammatory diseases and may be used as targets for novel treatments.
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“Different cellular lineages (10–18) may extrude their mitochondria upon activation.”
From Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA (2019) · cites this paper as [16]
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“Various cellular lineages are capable of extruding their mitochondria. Activated mast cells10, T-cells11, eosinophils12, hepatocytes13, neutrophils14–16 and platelets17,18, in addition to damaged organs or tissues7,13,19,20, release extracellular mitochondria.”
From Anti-mitochondrial autoantibodies in systemic lupus erythematosus and their association with disease manifestations (2019) · cites this paper as [10]
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- B Zhang, 2012, Preformed, but not de novo synthesized, TNF secretion from human mast cells is regulated by mitochondria, Int Arch Allergy Immunol
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Metadata
- Authors
- Zhang, B., Asadi, S., Weng, Z., Sismanopoulos, N., & Theoharides, T. C.
- Affiliations
- Tufts University (US)
- Corresponding author
- Theoharides, Theoharis C.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-12-17
- Volume
- 7
- Issue
- 12
- Pages
- e49767
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3524249
- OpenAlex
- W2169711067
- Cited by
- 121
- References
- 43
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 10 · 2023: 6 · 2022: 7 · 2021: 7 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 11 · 2016: 11 · 2015: 13 · 2014: 7 · 2013: 11
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR047652)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- mast cells, mitochondrial DNA, ATP, substance P, mast cell degranulation, LAD2 cells, histamine release, prostanoids, interleukin-8, TNF-α, IL-1β, vascular endothelial growth factor, keratinocytes, microvascular endothelial cells, compound 48/80, systemic circulation
- MeSH terms
- Animals, p-Methoxy-N-methylphenethylamine, DNA, Mitochondrial, Extracellular Space, Humans, Inflammation, Male, Mast Cells, Mitochondria, Cell Degranulation, Cytokines, Autocrine Communication, Paracrine Communication, Rats, Exosomes, Receptors, Purinergic P2X7, Inflammasomes
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