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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Different cellular lineages may extrude their mitochondria upon activation.
“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]
The Results section reports extracellular mitochondrial particles from stimulated human mast cells, supporting the claim for that lineage. The Introduction describes mitochondrial movement in T cells, not extrusion, and the Discussion mentions mtDNA in glioblastoma-cell exosomes without linking it to activation. The paper therefore does not establish extrusion upon activation across different cellular lineages. (LLM, conf=0.87)
Experimental — accuracy not yet measuredVarious activated cells and damaged tissues release extracellular mitochondria.
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Circulating mitochondrial DAMPs cause inflammatory responses to injury
Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010) · Nature · doi:10.1038/nature08780 · Cited by 3,812 · see citing works
Yang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,262 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794 · see citing works
Mitochondria: Dynamic Organelles in Disease, Aging, and Development
Chan, D. C. (2006) · Cell · doi:10.1016/j.cell.2006.06.010 · Cited by 1,987 · see citing works
Mast cells in the development of adaptive immune responses
Galli, S. J., Nakae, S., & Tsai, M. M. (2005) · Nature Immunology · doi:10.1038/ni1158 · Cited by 1,280 · see citing works
Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin
Gordon, J., & Galli, S. J. (1990) · Nature · doi:10.1038/346274a0 · Cited by 989 · see citing works
Mast cell-orchestrated immunity to pathogens
Abraham, S. N., & John, A. L. S. (2010) · Nature reviews. Immunology · doi:10.1038/nri2782 · Cited by 959 · see citing works
Mitochondrial fission in apoptosis
Youle, R. J., & Karbowski, M. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1697 · Cited by 773 · see citing works
Theoharides, T. C., Alysandratos, K., Angelidou, A., Delivanis, D.-A., Sismanopoulos, N., Zhang, B., Asadi, S., Vasiadi, M., Weng, Z., Miniati, A., et al. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.12.014 · Cited by 759 · see citing works
Self-citationAstrocytes and Glioblastoma cells release exosomes carrying mtDNA
Guescini, M., Genedani, S., Stocchi, V., & Agnati, L. F. (2009) · Journal of Neural Transmission · doi:10.1007/s00702-009-0288-8 · Cited by 662 · see citing works
Valent, P., Akin, C., Arock, M., Brockow, K., Butterfield, J. H., Carter, M. C., Castells, M., Escribano, L., Hartmann, K., Lieberman, P., et al. (2012) · International Archives of Allergy and Immunology · doi:10.1159/000328760 · Cited by 654 · see citing works
Mitochondrial fusion, fission and autophagy as a quality control axis: The bioenergetic view
Twig, G., Hyde, B. B., & Shirihai, O. S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.05.001 · Cited by 646 · see citing works
DNA released from dying host cells mediates aluminum adjuvant activity
Marichal, T., Ohata, K., Bedoret, D., Mesnil, C., Sabatel, C. M., Kobiyama, K., Lekeux, P. M., Coban, C., Akira, S., Ishii, K. J., et al. (2011) · Nature Medicine · doi:10.1038/nm.2403 · Cited by 538 · see citing works
Kirshenbaum, A. S., Akin, C., Wu, Y., Rottem, M., Goff, J. P., Beaven, M. A., Rao, V. K., & Metcalfe, D. D. (2003) · Leukemia Research · doi:10.1016/s0145-2126(02)00343-0 · Cited by 513 · see citing works
Kouzaki, H., Iijima, K., Kobayashi, T., O’Grady, S. M., & Kita, H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003020 · Cited by 494 · see citing works
The in-depth evaluation of suspected mitochondrial disease
Haas, R., Parikh, S., Falk, M. J., Saneto, R. P., Wolf, N. I., Darín, N., Wong, L.-J. C., Cohen, B. H., & Naviaux, R. K. (2008) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2007.11.018 · Cited by 363 · see citing works
MITOCHONDRIAL DNA IS RELEASED BY SHOCK AND ACTIVATES NEUTROPHILS VIA P38 MAP KINASE
Zhang, Q., Itagaki, K., & Hauser, C. J. (2010) · Shock · doi:10.1097/shk.0b013e3181cd8c08 · Cited by 354 · see citing works
T cell activation requires mitochondrial translocation to the immunological synapse
Quintana, A., Schwindling, C., Wenning, A. S., Becherer, U., Rettig, J., Schwarz, E. C., & Hoth, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703126104 · Cited by 347 · see citing works
Roles of mast cells and basophils in innate and acquired immunity
Wedemeyer, J., Tsai, M. M., & Galli, S. J. (2000) · Current Opinion in Immunology · doi:10.1016/s0952-7915(00)00154-0 · Cited by 345 · see citing works
Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation
Corriden, R., & Insel, P. A. (2010) · Science Signaling · doi:10.1126/scisignal.3104re1 · Cited by 338 · see citing works
Skokos, D., Panse, S. L., Villa, I., Rousselle, J.-C., Péronet, R., David, B., Namane, A., & Mécheri, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.2.868 · Cited by 333 · see citing works
Orchestration of lymphocyte chemotaxis by mitochondrial dynamics
Campello, S., Lacalle, R. A., Bettella, M., Mañes, S., Scorrano, L., & Viola, A. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20061877 · Cited by 325 · see citing works
The Critical Role of Mast Cells in Allergy and Inflammation
Theoharides, T. C., & Kalogeromitros, D. C. (2006) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1366.025 · Cited by 291 · see citing works
Self-citationSleep in Children With Autism Spectrum Disorder
Kotagal, S., & Broomall, E. M. (2012) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2012.05.007 · Cited by 271 · see citing works
Diagnosis and Treatment of Cutaneous Mastocytosis in Children
Castells, M., Metcalfe, D. D., & Escribano, L. (2011) · American Journal of Clinical Dermatology · doi:10.2165/11588890-000000000-00000 · Cited by 193 · see citing works
Weng, Z., Zhang, B., Asadi, S., Sismanopoulos, N., Butcher, A., Fu, X., Katsarou‐Katsari, A., Antoniou, C., & Theoharides, T. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033805 · Cited by 189 · see citing works
Self-citationHuman mast cells, bacteria, and intestinal immunity
Bischoff, S. C., & Krämer, S. (2007) · Immunological Reviews · doi:10.1111/j.1600-065x.2007.00523.x · Cited by 164 · see citing works
TNF Trafficking to Human Mast Cell Granules: Mature Chain-Dependent Endocytosis
Olszewski, M. B., Groot, A. J., Dastych, J., & Knol, E. F. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5701 · Cited by 151 · see citing works
Zhang, B., Alysandratos, K., Angelidou, A., Asadi, S., Sismanopoulos, N., Delivanis, D.-A., Weng, Z., Miniati, A., Vasiadi, M., Katsarou‐Katsari, A., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.02.005 · Cited by 142 · see citing works
Self-citationCharacterization of Mast Cell-Committed Progenitors Present in Human Umbilical Cord Blood
Kempuraj, D., Saito, H., Kaneko, A., Fukagawa, K., Nakayama, M., Toru, H., Tomikawa, M., Tachimoto, H., Ebisawa, M., Akasawa, A., et al. (1999) · Blood · doi:10.1182/blood.v93.10.3338.410k05_3338_3346 · Cited by 110 · see citing works
The internal pH of mast cell granules
Johnson, R. G., Carty, S. E., Fingerhood, B. J., & Scarpa, A. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)81050-7 · Cited by 93 · see citing works
Mitochondrial DNA and anti-mitochondrial antibodies in serum of autistic children
Zhang, B., Angelidou, A., Alysandratos, K., Vasiadi, M., Francis, K., Asadi, S., Theoharides, A., Sideri, K., Lykouras, L., Kalogeromitros, D. C., et al. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-80 · Cited by 93 · see citing works
Self-citationSismanopoulos, N., Delivanis, D. A., Alysandratos, K., Angelidou, A., Vasiadi, M., Therianou, A., & Theoharides, T. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033271 · Cited by 82 · see citing works
Self-citationAutism Spectrum Disorders and Mastocytosis
Theoharides, T. C. (2009) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463200902200401 · Cited by 79 · see citing works
Self-citationAutism: an emerging ‘neuroimmune disorder’ in search of therapy
Theoharides, T. C., Kempuraj, D., & Redwood, L. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560903107789 · Cited by 79 · see citing works
Self-citationAngelidou, A., Alysandratos, K., Asadi, S., Zhang, B., Francis, K., Vasiadi, M., Kalogeromitros, D. C., & Theoharides, T. C. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1171-z · Cited by 64 · see citing works
Self-citationLauritzen, K. H., Moldestad, O., Eide, L., Carlsen, H., Nesse, G., Storm, J. F., Mansuy, I. M., Bergersen, L. H., & Klungland, A. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.01149-09 · Cited by 60 · see citing works
Sudo, N., Tanaka, K., Koga, Y., Okumura, Y., Kubo, C., & Nomoto, K. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.156.10.3970 · Cited by 45 · see citing works
Zhang, B., Weng, Z., Sismanopoulos, N., Asadi, S., Therianou, A., Alysandratos, K., Angelidou, A., Shirihai, O. S., & Theoharides, T. C. (2012) · International Archives of Allergy and Immunology · doi:10.1159/000335178 · Cited by 39 · see citing works
Self-citationNeuropeptide blood levels correlate with mast cell load in patients with mastocytosis
Maintz, L., Wardelmann, E., Walgenbach, K. J., Fimmers, R., Bieber, T. R. M., Raap, U., & Novak, N. (2011) · Allergy · doi:10.1111/j.1398-9995.2011.02550.x · Cited by 28 · see citing works
Schaechter, M. (2012) · Science · doi:10.1126/science.1218027 · Cited by 11 · see citing works
Zhang, B., Alysandratos, K., Angelidou, A., Kempuraj, D., Tagen, M., Vasiadi, M., Asadi, S., & Theoharides, T. C. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.184.supp.135.11 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Haraszti, R. A., Didiot, M., Sapp, E., Leszyk, J., Shaffer, S. A., Rockwell, H. E., Gao, F., Narain, N. R., DiFiglia, M., Kiebish, M. A., et al. (2016) · Journal of Extracellular Vesicles · doi:10.3402/jev.v5.32570 · Cited by 746 · see citing works
Boudreau, L. H., Duchez, A.-C., Cloutier, N., Soulet, D., Martin, N., Bollinger, J., Paré, A., Rousseau, M., Naika, G. S., Lévesque, T., et al. (2014) · Blood · doi:10.1182/blood-2014-05-573543 · Cited by 703 · see citing works
Petra, A. I., Panagiotidou, S., Hatziagelaki, E., Stewart, J. M., Conti, P., & Theoharides, T. C. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.04.002 · Cited by 592 · see citing works
Self-citationMast Cells, Mastocytosis, and Related Disorders
Theoharides, T. C., Valent, P., & Akin, C. (2015) · New England Journal of Medicine · doi:10.1056/nejmra1409760 · Cited by 518 · see citing works
Self-citationKey role of CRF in the skin stress response system
Slominski, A. T., Zmijewski, M. A., Zbytek, B., Tobin, D. J., Theoharides, T. C., & Rivier, J. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1092 · Cited by 400 · see citing works
Self-citationThe Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases
Nakahira, K., Hisata, S., & Choi, A. M. K. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6407 · Cited by 363 · see citing works
Mitochondrial DNA Release in Innate Immune Signaling
Newman, L. E., & Shadel, G. S. (2023) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-104401 · Cited by 331 · see citing works
Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX
Ney, P. A. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.02.022 · Cited by 319 · see citing works
Mast cells in neuroinflammation and brain disorders
Hendriksen, E., van Bergeijk, D. A., Oosting, R. S., & Redegeld, F. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.05.001 · Cited by 240 · see citing works
Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders
Theoharides, T. C., Tsilioni, I., Patel, A., & Doyle, R. (2016) · Translational Psychiatry · doi:10.1038/tp.2016.77 · Cited by 231 · see citing works
Self-citationLong‐COVID syndrome‐associated brain fog and chemofog: Luteolin to the rescue
Theoharides, T. C., Cholevas, C., Polyzoidis, K. S., & Politis, A. M. (2021) · BioFactors · doi:10.1002/biof.1726 · Cited by 219 · see citing works
Self-citationFocal brain inflammation and autism
Theoharides, T. C., Asadi, S., & Patel, A. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-46 · Cited by 178 · see citing works
Self-citationTheoharides, T. C. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00225 · Cited by 154 · see citing works
Self-citationMast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome
Theoharides, T. C., Tsilioni, I., & Bawazeer, M. A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00353 · Cited by 150 · see citing works
Self-citationThe diversity of platelet microparticles
Boilard, É., Duchez, A., & Brisson, A. R. (2015) · Current Opinion in Hematology · doi:10.1097/moh.0000000000000166 · Cited by 144 · see citing works
Diagnostic and therapeutic potentials of exosomes in CNS diseases
Kawiková, I., & Askenase, P. W. (2014) · Brain Research · doi:10.1016/j.brainres.2014.09.070 · Cited by 144 · see citing works
Mast cells, brain inflammation and autism
Theoharides, T. C., Stewart, J. M., Panagiotidou, S., & Melamed, I. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.03.086 · Cited by 138 · see citing works
Self-citationPlatelets release mitochondrial antigens in systemic lupus erythematosus
Melki, I., Allaeys, I., Tessandier, N., Lévesque, T., Cloutier, N., Laroche, A., Vernoux, N., Becker, Y., Benk-Fortin, H., Zufferey, A., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.aav5928 · Cited by 125 · see citing works
Theoharides, T. C., Tsilioni, I., & Ren, H. L. (2019) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2019.1596800 · Cited by 124 · see citing works
Self-citationNeuroendocrinology of mast cells: Challenges and controversies
Theoharides, T. C. (2017) · Experimental Dermatology · doi:10.1111/exd.13288 · Cited by 117 · see citing works
Self-citationMitoEVs: A new player in multiple disease pathology and treatment
Zhou, X., Liu, S., Lu, Y., Wan, M., Cheng, J., & Liu, J. (2023) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12320 · Cited by 113 · see citing works
Malla, R. R., Pandrangi, S. L., Kumari, S., Gavara, M. M., & Badana, A. K. (2018) · Asia-Pacific Journal of Clinical Oncology · doi:10.1111/ajco.12869 · Cited by 105 · see citing works
Mitochondrial Stress Signaling Promotes Cellular Adaptations
Barbour, J. A., & Turner, N. A. (2014) · International Journal of Cell Biology · doi:10.1155/2014/156020 · Cited by 102 · see citing works
Mitochondrial function and abnormalities implicated in the pathogenesis of ASD
Castora, F. J. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.12.015 · Cited by 104 · see citing works
Taracanova, A., Tsilioni, I., Conti, P., Norwitz, E. R., Leeman, S. E., & Theoharides, T. C. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1810133115 · Cited by 92 · see citing works
Self-citationFibromyalgia Syndrome in Need of Effective Treatments
Theoharides, T. C., Tsilioni, I., Arbetman, L., Panagiotidou, S., Stewart, J. M., Gleason, R. M., & Russell, I. J. (2015) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.115.227298 · Cited by 86 · see citing works
Self-citationRoles of secreted phospholipase A2 group IIA in inflammation and host defense
Doré, É., & Boilard, É. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.08.017 · Cited by 84 · see citing works
The Role of Mast Cells in Irritable Bowel Syndrome
Lee, K. N., & Lee, O. Y. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/2031480 · Cited by 88 · see citing works
Decoding Mast Cell-Microglia Communication in Neurodegenerative Diseases
Sandhu, J. K., & Kulka, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031093 · Cited by 85 · see citing works
Stress triggers coronary mast cells leading to cardiac events
Alevizos, M., Karagkouni, A., Panagiotidou, S., Vasiadi, M., & Theoharides, T. C. (2013) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2013.09.017 · Cited by 83 · see citing works
Self-citationJung, J. E., Sun, G., Bautista-Garrido, J., Obertas, L., Mobley, A. S., Ting, S., Zhao, X., & Aronowski, J. A. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.2212-19.2020 · Cited by 80 · see citing works
Becker, Y., Loignon, R.-C., Julien, A.-S., Marcoux, G., Allaeys, I., Lévesque, T., Rollet-Labelle, E., Benk-Fortin, H., Cloutier, N., Melki, I., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-40900-3 · Cited by 75 · see citing works
Lauritano, D., Mastrangelo, F., D’Ovidio, C., Ronconi, G., Caraffa, A., Gallenga, C. E., Frydas, I., Kritas, S. K., Trimarchi, M., Carinci, F., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054811 · Cited by 76 · see citing works
Theoharides, T. C., & Kempuraj, D. (2023) · Cells · doi:10.3390/cells12050688 · Cited by 81 · see citing works
Self-citationHeme as a danger molecule in pathogen recognition
Wegiel, B., Hauser, C. J., & Otterbein, L. E. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.08.020 · Cited by 72 · see citing works
Sources of Pathogenic Nucleic Acids in Systemic Lupus Erythematosus
Mustelin, T., Lood, C., & Giltiay, N. V. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01028 · Cited by 68 · see citing works
Is a Subtype of Autism an Allergy of the Brain?
Theoharides, T. C. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.04.009 · Cited by 65 · see citing works
Self-citationHatziagelaki, E., Adamaki, M., Tsilioni, I., Dimitriadis, G., & Theoharides, T. C. (2018) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.118.250845 · Cited by 62 · see citing works
Exosomes: Nanocarriers of Biological Messages
Conigliaro, A., Fontana, S., Raimondo, S., & Alessandro, R. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-981-10-4397-0_2 · Cited by 62 · see citing works
Autoantibodies in Systemic Lupus Erythematosus Target Mitochondrial RNA
Becker, Y., Marcoux, G., Allaeys, I., Julien, A.-S., Loignon, R.-C., Benk-Fortin, H., Rollet-Labelle, E., Rauch, J., Fortin, P. R., & Boilard, E. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01026 · Cited by 59 · see citing works
Immunoregulatory effect of mast cells influenced by microbes in neurodegenerative diseases
Girolamo, F., Coppola, C., & Ribatti, D. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.06.017 · Cited by 60 · see citing works
Neuroendocrinology of the skin
Theoharides, T. C., Stewart, J. M., Taracanova, A., Conti, P., & Zouboulis, C. C. (2016) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-016-9369-9 · Cited by 58 · see citing works
Self-citationSherrill, J. D., Kiran, K. C., Wang, X., Wen, T., Chamberlin, A. C., Stucke, E. M., Collins, M. H., Abonia, J. P., Peng, Y., Wu, Q., et al. (2018) · JCI Insight · doi:10.1172/jci.insight.99922 · Cited by 56 · see citing works
Theoharides, T. C., Athanassiou, M. C., Panagiotidou, S., & Doyle, R. (2014) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2014.12.003 · Cited by 56 · see citing works
Self-citationSpectrum of mast cell activation disorders
Petra, A. I., Panagiotidou, S., Stewart, J. M., Conti, P., & Theoharides, T. C. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.906302 · Cited by 54 · see citing works
Self-citationTherianou, A., Vasiadi, M., Delivanis, D. A., Petrakopoulou, T., Katsarou‐Katsari, A., Antoniou, C., Stratigos, A., Tsilioni, I., Katsambas, A., Rigopoulos, D., et al. (2018) · Experimental Dermatology · doi:10.1111/exd.13831 · Cited by 54 · see citing works
Self-citationMast Cells, Stress, Fear and Autism Spectrum Disorder
Theoharides, T. C., Kavalioti, M., & Tsilioni, I. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153611 · Cited by 55 · see citing works
Self-citationPatel, A., & Theoharides, T. C. (2017) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.117.240564 · Cited by 54 · see citing works
Self-citationPetra, A. I., Tsilioni, I., Taracanova, A., Katsarou‐Katsari, A., & Theoharides, T. C. (2018) · Allergy and Asthma Proceedings · doi:10.2500/aap.2018.38.4105 · Cited by 54 · see citing works
Self-citationTheoharides, T. C., Twahir, A., & Kempuraj, D. (2023) · Annals of Allergy Asthma & Immunology · doi:10.1016/j.anai.2023.10.032 · Cited by 54 · see citing works
Self-citationTheoharides, T. C., Asadi, S., Panagiotidou, S., & Weng, Z. (2013) · Autoimmunity Reviews · doi:10.1016/j.autrev.2013.06.018 · Cited by 48 · see citing works
Self-citationSingh, B., Modica-Napolitano, J. S., & Singh, K. K. (2017) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2017.05.004 · Cited by 49 · see citing works
A systematic review of gut‐immune‐brain mechanisms in Autism Spectrum Disorder
Azhari, A., Azizan, F., & Esposito, G. (2018) · Developmental Psychobiology · doi:10.1002/dev.21803 · Cited by 47 · see citing works
Neutrophil Extracellular Traps in Asthma: Friends or Foes?
Poto, R., Shamji, M. H., Marone, G., Durham, S. R., Scadding, G. W., & Varricchi, G. (2022) · Cells · doi:10.3390/cells11213521 · Cited by 47 · see citing works
Marabitti, V., Vulpis, E., Nazio, F., & Campello, S. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107382 · Cited by 44 · see citing works
Stortz, J. A., Hawkins, R. B., Holden, D. C., Raymond, S. L., Wang, Z., Brakenridge, S. C., Cuschieri, J., Moore, F. A., Maier, R. V., Moldawer, L. L., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-50044-z · Cited by 42 · see citing works
Impact of Mast Cells on the Skin
Kritas, S. K., Saggini, A., Varvara, G., Murmura, G., Caraffa, A., Antinolfi, P., Toniato, E., Pantalone, A., Neri, G., Frydas, S., et al. (2013) · International Journal of Immunopathology and Pharmacology · doi:10.1177/039463201302600403 · Cited by 39 · see citing works
Self-citationMitochondrial Bioenergetics and Dynamics in Secretion Processes
Martínez, J., Marmisolle, I., Tarallo, D., & Quijano, C. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00319 · Cited by 38 · see citing works
Aguirre, A., Maturana, C. J., Harcha, P. A., & Sáez, J. C. (2013) · Mediators of Inflammation · doi:10.1155/2013/893521 · Cited by 37 · see citing works
Autism and EMF? Plausibility of a pathophysiological link – Part I
Herbert, M. R., & Sage, C. (2013) · Pathophysiology · doi:10.1016/j.pathophys.2013.08.001 · Cited by 35 · see citing works
Chen, H., Chiang, D. M., Lin, Z.-J., Hsieh, C., Yin, G.-C., Weng, I., Guttmann, P., Werner, S., Henzler, K. D., Schneider, G., et al. (2016) · Scientific Reports · doi:10.1038/srep34879 · Cited by 36 · see citing works
The Role Played by Mitochondria in FcεRI-Dependent Mast Cell Activation
Chelombitko, M. A., Chernyak, B. V., Fedorov, A. V., Zinovkin, R. A., Razin, E., & Paruchuru, L. B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.584210 · Cited by 34 · see citing works
Atopic Conditions in Search of Pathogenesis and Therapy
Theoharides, T. C. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.04.002 · Cited by 34 · see citing works
Self-citationToyoshima, S., Sakamoto-Sasaki, T., Kurosawa, Y., Hayama, K., Matsuda, A., Watanabe, Y., Terui, T., Gon, Y., Matsumoto, K., & Okayama, Y. (2021) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2021.01.002 · Cited by 33 · see citing works
Mitochondrial Extracellular Vesicles: A Promising Avenue for Diagnosing and Treating Lung Diseases
Ding, F., Zhou, M., Ren, Y., Li, Y., Xiang, J., Li, Y., Yu, J., Hong, Y., Fu, Z., Li, H., et al. (2024) · ACS Nano · doi:10.1021/acsnano.4c02940 · Cited by 34 · see citing works
Mitochondrial regulation in the tumor microenvironment: targeting mitochondria for immunotherapy
Ahn, M., Ali, A., & Seo, J. H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1453886 · Cited by 33 · see citing works
Maldonado‐Ruiz, R., Garza‐Ocañas, L., & Camacho‐Morales, A. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.03.009 · Cited by 30 · see citing works
Nanotube Formation: A Rapid Form of “Alarm Signaling”?
Weng, Z., Zhang, B., Tsilioni, I., & Theoharides, T. C. (2016) · Clinical Therapeutics · doi:10.1016/j.clinthera.2016.02.030 · Cited by 30 · see citing works
Self-citationTheoharides, T. C. (2021) · Journal of Personalized Medicine · doi:10.3390/jpm11090860 · Cited by 29 · see citing works
Self-citationVaried Composition and Underlying Mechanisms of Gut Microbiome in Neuroinflammation
Farooq, R. K., Alamoudi, W., Alhibshi, A., Rehman, S., Sharma, A. R., & Abdulla, F. A. (2022) · Microorganisms · doi:10.3390/microorganisms10040705 · Cited by 30 · see citing works
Emerging roles of mitochondria and autophagy in liver injury during sepsis
Aki, T., Unuma, K., & Uemura, K. (2017) · Cell Stress · doi:10.15698/cst2017.11.110 · Cited by 28 · see citing works
Mast cell activation: beyond histamine and tryptase
Theoharides, T. C., Perlman, A. I., Twahir, A., & Kempuraj, D. (2023) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2023.2200936 · Cited by 27 · see citing works
Self-citationAutism and EMF? Plausibility of a pathophysiological link part II
Herbert, M. R., & Sage, C. (2013) · Pathophysiology · doi:10.1016/j.pathophys.2013.08.002 · Cited by 27 · see citing works
Mitoptosis, Twenty Years After
Lyamzaev, K. G., Кнорре, Д. А., & Chernyak, B. V. (2020) · Biochemistry (Moscow) · doi:10.1134/s0006297920120020 · Cited by 21 · see citing works
Tsilioni, I., Natelson, B. H., & Theoharides, T. C. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15828 · Cited by 20 · see citing works
Self-citationPiotin, A., Oulehri, W., Charles, A., Tacquard, C. A., Collange, O., Mertès, P., & Gény, B. (2024) · Antioxidants · doi:10.3390/antiox13080920 · Cited by 20 · see citing works
Horbay, R., Syrvatka, V. J., Bedzai, A. O., van der Merwe, M., Burger, D. E., & Beug, S. T. (2025) · Journal of Extracellular Vesicles · doi:10.1002/jev2.70192 · Cited by 20 · see citing works
Risha, Y., Susevski, V., Hüttmann, N., Poolsup, S., Minić, Z., & Berezovski, M. V. (2021) · Biomedicines · doi:10.3390/biomedicines9020107 · Cited by 19 · see citing works
Polyakova, V. O., Kvetnoy, I. M., Anderson, G., Rosati, J. D., Mazzoccoli, G., & Linkova, N. S. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00199 · Cited by 19 · see citing works
Extracellular Mitochondria in Traumatic Brain Injury Induced Coagulopathy
Zhao, Z., Zhou, Y., Li, M., Zhang, J., & Dong, J. (2019) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0039-3402427 · Cited by 19 · see citing works
n-3 Polyunsaturated fatty acids and mast cell activation
Wang, X., & Kulka, M. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.2ru0814-388r · Cited by 16 · see citing works
Wang, Z., Hou, Y., Sun, H., Wang, Z., & Zhang, H. (2024) · Medicine · doi:10.1097/md.0000000000040207 · Cited by 15 · see citing works
Morciano, G., Pellielo, G., Agyapong, E. D., Pellegrino, C., Patergnani, S., Franceschini, D., Koutsikos, K., Rigon, L., Pinton, P., & Rimessi, A. (2026) · Journal of Translational Medicine · doi:10.1186/s12967-026-07783-1 · Cited by 17 · see citing works
Multifaceted roles of mitochondria in asthma
Zhang, W., Zhang, C., Zhang, Y., Zhou, X., Dong, B., Tan, H., Su, H., & Sun, X. (2024) · Cell Biology and Toxicology · doi:10.1007/s10565-024-09928-8 · Cited by 14 · see citing works
Mast Cells in Autism Spectrum Disorder—The Enigma to Be Solved?
Kovacheva, E., Gevezova, M., Maes, M. H. J., & Sarafian, V. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052651 · Cited by 12 · see citing works
Biogenesis and homeostasis of mast cell lysosome related secretory granules
Sagi‐Eisenberg, R. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1603999 · Cited by 11 · see citing works
Extracellular Mitochondrial ATP, Suramin, and Autism?
Theoharides, T. C. (2013) · Clinical Therapeutics · doi:10.1016/j.clinthera.2013.07.419 · Cited by 10 · see citing works
Self-citationMarutani, T., Nishino, K., Miyaji, T., Kamada, K., Ohura, K., Kiso, Y., & Mukai, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084084 · Cited by 10 · see citing works
Unveiling Leukocyte Extracellular Traps in Inflammatory Responses of the Central Nervous System
Colciaghi, F., & Costanza, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.915392 · Cited by 9 · see citing works
Target Therapies for Systemic Mastocytosis: An Update
Sciumé, M., Magistris, C. D., Galli, N., Ferretti, E., Milesi, G., Roberto, P. D., Fabris, S., & Grifoni, F. I. (2022) · Pharmaceuticals · doi:10.3390/ph15060738 · Cited by 11 · see citing works
Marutani, T., Hattori, T., Tsutsumi, K., Koike, Y., Harada, A., Noguchi, K., Kiso, Y., & Mukai, H. (2015) · Biopolymers · doi:10.1002/bip.22788 · Cited by 9 · see citing works
Abal, M. (2017) · Annals of Translational Medicine · doi:10.21037/atm.2017.03.48 · Cited by 9 · see citing works
Expanding the Immunologic and Neuronal Landscape of IgE‐Mediated Anaphylaxis
Biswas, R., Fried, J. M., & de Lafaille, M. A. C. (2025) · Immunological Reviews · doi:10.1111/imr.70078 · Cited by 8 · see citing works
Mitochondrial genome association study with peripheral arterial disease and venous thromboembolism
Abrantes, P., Rosa, A., Francisco, V., Sousa, I., Xavier, J. M., & Oliveira, S. A. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.07.920 · Cited by 8 · see citing works
Mitochondrial damage‐associated molecular patterns in blood transfusion products
Marcoux, G., & Boilard, É. (2017) · ISBT Science Series · doi:10.1111/voxs.12381 · Cited by 8 · see citing works
The Role of Mast Cells in Autism Spectrum Disorder.
Priego-González, L., Pardo, P. P., & Redegeld, F. (2025) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106263 · Cited by 7 · see citing works
Neurodevelopmental disorders: 2022 update
Sabariego-Navarro, M., Fernández‐Blanco, Á., Sierra, C., & Dierssen, M. (2022) · Free Neuropathology · doi:10.17879/freeneuropathology-2022-3801 · Cited by 7 · see citing works
The Clinical Relevance of Mast Cell Activation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Rohrhofer, J., Ebner, L., Schweighardt, J., Stingl, M., & Untersmayr, E. (2025) · Diagnostics · doi:10.3390/diagnostics15222828 · Cited by 6 · see citing works
Cuong, D. V., Kim, H. K., Marquez, J. C., Kim, N., Ko, K. S., Rhee, B. D., & Han, J. (2016) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2016.20.2.213 · Cited by 6 · see citing works
Extracellular mitochondrial components as new biomarkers for lupus nephritis
Gowda, S., Rana, K., Kumar, A., Prajapati, P. K., Patel, N., Pandya, S. C., & Srivastava, R. (2024) · Lupus · doi:10.1177/09612033241247622 · Cited by 5 · see citing works
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
